Chapter 15 Chemical Coordination and Integration by TEACHING CARE online tuition and coaching classes

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Introduction : Endocrine system formed of all endocrine glands of body. Though different endocrine glands are different in embryonic origin and are isolated from one another but these interact with one another so collectively form an endocrine system. Endocrine system along with nervous system, controls and coordinates the body functions and maintains a homeostais. So both are collectively form neuro-endocrine system. The study of these two systems is called neuro-endocrinology.

The nervous system achieves functional co-ordination and integration for quick responses of body, like a high- speed service. Contrarily, the endocrine system achieves co-ordination and integration for slow responses of body, like a low speed service.

Glands of body : A cell, a tissue or an organ which secretes certain useful chemical compounds is called a gland. Animals have three types of glands.

Exocrine gland (Gr., ex = out + krinein = to secrete) : These glands have ducts for discharging their Therefore, they called duct glands. ex – Liver, Sweat gland, Sebaceous gland, Gastric glands and some intestinal glands.
Endocrine glands ( Gr., endo = within + krinein = to secrete) : These glands lack ducts and pass secretions into the surrounding blood directly. Therefore they called ductless glands. ex – Thyroid, parathyroid, adrenal, pituitary, pineal body and thymus.
Heterocrine glands : These glands consist of both exocrine and endocrine tissue. The exocrine discharge its secretion by a duct and the endocrine tissue discharge its secretion into the blood. Pancreas and gonads are heterocrine glands. These are also called mixed

Hormones and their mechanism

Hormones are informational molecules secreted by the endocrine cells in one part of the body and carried by blood to another part where they stimulate or inhibit specific physiological process. In other words the hormones are chemical messengers or informational molecules that regulate the biological processes and metabolism. Hormones organs called target organs. Targate cells have receptor proteins for specific hormone.

Discovery : First hormone discovered was secretin. It was discovered by two English physiologists : William M Bayliss and Ernest H. Starling in 1903.

Nomenclature : Term hormone was coined by starling (1905) from Greek work Hormaein means to excite.

It is a mishomer because a number of hormones are known to have inhibitory effect (e.g. Somatostatin)

(i) Properties of hormones

These are secreted by endocrine gland (biogenic in origin).
Their secretions is released directly into blood (except local hormones g. gastrin).
These are carried to distantly located specific organs, called target
These have specific physiological action (excitatory or inhibatory). These co-ordinate different physical, mental and metabolic activities and maintain
The hormones have low molecular weight g. ADH has a molecular weight of 600–2000 daltons.
These act in very low concentration g. around10^–10 molar.
Hormones are non

These are mostly short-lived. So have a no camulative
Some hormones are quick acting g. adrenalin, while some acting slowly e.g. ostrogen of ovary.
Some hormones secreted in inactive form called Prohormone g. Pro-insulin.
Hormones are They are carriers of specific information to their specific target organ. Only those target cell respond to a particular hormone for which they have receptors.

(ii) Classification of hormones

On the basis of chemical nature : On the basis of chemical composition hormones are classified into three

Amine hormones : These are derived form tyrosine amino acid and have amino (- NH2 )

Thyroxine, Epinephrine, Nor-epinephrine.

group e.g.

Steroids : These are fat soluble and have sterol group. These are derived from cholesterol g. hormones of adrenal cortex (cartisol, cartisone, carticasterone, aldasterone) testes (testosterone etc.) and ovaries (estrone, estradiol, progesterone etc.)
Proteinous and peptide hormones : These are formed of 3 – 200 amino acids interlinked by peptide bonds and are water soluble g.

Proteinous hormones like STH, TSH, FSH, LH Out of these FSH and LH are glycoproteins.
Long peptide hormones like insulin and glucagon, ACTH, Paratharmone.
Short peptide hormones like oxytocin, ADH, MSH. These hormones formed of a few amino

(b) On the basis of mode of action

Quick acting hormones : These hormones initiate immediate response from their target cells. There receptor is always located on the outer surface of plasma membrane of target cell because these are large Hormone receptor complex activates a membrane enzyme adenyl cyclase which hydrolise ATP into cyclic AMP. Which acts as secondary messenger, c-AMP activates an inactive enzyme system by cassade effect. So their mode of action is called second messenger hypothesis. e.g. These includes proteinous, peptide and amine hormones.
Short acting hormones : These hormones intiate response after some time. These are small sized so are diffusable through the plasma membrane of their target These bind their proteinous receptor present in the cytosol. These always operate through de-novo synthesis of m-RNA by activation of certain genes. So their mechanism of action is called m-RNA hypothesis. e.g. These include steroid hormones of testes, ovary and adrenal cortex.

Differences between hormone and enzymes : Though both hormones and enzymes regulate the body functions, but they have following

S.No.	Characters	Enzymes	Hormones
1.	Chemistry	Always proteinaceous	May be proteinaceous, or amine or steroids.
2.	Molecular weight	Macromolecules with high molecular weights.	Have low molecular weights.
3.	Diffusibility	Non-diffusible through cell membrane.	Diffusible through cell membrane.
4.	Site of action	Either act intracellularly or carried by some duct to another site.	Generally carried by blood to a target organ.
5.	Mode of action	Always act as biocatalysts and increase the rate of metabolic physiological process.	May be excitatory or inhibitatory in their physiological action.
6.	Reversibility	These catalyze reversible reactions.	Hormone controlled reactions are not reversible.

7.	Effect of concentration	Reaction rate increase with increase in their concentration upto a limit.	Deficiency or excess of hormone causes metabolic disorders and diseases.
8.	Speed	Act quickly	Some are quick acting, while some are slow acting with a lag period.
9.	Consumption	Not used in metabolic functions.	Used up in metabolic functions.

Difference between hormone and vitamin : Though both hormones and vitamins are similar in being organic (compounds; required in micro-amount and regulate the metabolic functions, but two also differ in a number of

S.No.	Characters	Hormones	Vitamins
1.	Source	Synthesized in the endocrine cells of body.	Taken along with food from outside.
2.	Chemistry	Steroids or proteinous or amino acid derivatives.	Simple organic compounds like amines, esters, organic acids etc.
3.	Action	Either excitatory or inhibatory. Do not act as co- enzymes.	These generally act as co-enzymes for enzyme activity.
4.	Cause of disorders	Both excess as well as deficiency of hormones.	Generally avitaminosis (deficiency of vitamins) leads to deficiency diseases.

Differences between nervous and hormonal informations : Both hormonal and nervous system control and coordinate the body functions and work in co-ordination to maintain a steady state condition, called But two types of controls differ in some important characters.

S.No.	Characters	Nervous control	Hormones control
1.	Speed of action	Always quick acting.	May be quick acting or acting with a long period.
2.	Mode of transmission of informations	As electrochemical nerve impulses.	As chemical messengers.
3.	Path of transmission	Through nerve fibres.	Through blood.
4.	Direction of the informations	Towards a specific direction (effector organ or CNS).	Released in general blood circulation from where taken by specific receptor.
5.	Suitability	For quick reactions like reflexes.	For long-term changes e.g. maintenance of pregnancy.
6.	Durability	Short time effect.	Long lasting.

Release of hormones : Hormones are released from endocrine glands by three types of
Specific metabolic : The presence of a specific metabolite in the blood elicits the hormone to deal with For instance excess of glucose in the blood causes the release of insulin from the pancreas.
Other hormone : The presence of a specific hormone in the blood induces the release of another For example TSH stimulate thyroid gland to release thyroxine hormone.
Neuronal impulse : Neurons of autonomic system stimulate hormone release from some glands. For example adrenaline and nor-adrenaline are released from adrenal medulla on the arrival of nerve impulses during anxiety, stress and
Mechanism of hormone action : The hormones act in two ways –

On cell surface and within a cell.

On cell surface : The molecules of hormones that are amino acid derivatives, peptides or proteins are large and insoluble in lipid, and can not enter the target Therefore they act at the cell surface. They bind to specific receptor molecules located on the surface of cell membrane. The hormone receptor complex may acts in one of the two ways –
- Formation of cAMP : Mechanism of formation of cAMP was discovered by W. Sutherland in 1950. The hormone receptor complex causes the release of an enzyme adenyl cyclase. From the receptor site. This enzyme hydrolise the ATP into c-AMP. The c-AMP activates the existing enzyme system of the cell. This accelerates the metabolic reactions in cell. The hormone is called first messenger and the c-AMP is termed the second messenger. e.g. Adrenaline causes the secretion of glucose from the liver cell from this mechanism.

HORMONE (FIRST MESSENGER)

Fig. – Mechanism of Hormone action on cell surface

STEROID HORMONES

THYROID HORMONES

Fig. – Mechanism of cell surface within a cell

Change in membrane permeability : The receptor proteins of some hormones are large transmembrane intrinsic protein acting as ion channels for facilitated diffusion of Na⁺, K⁺, Ca²⁺ On binding with specific hormone these receptor proteins undergo conformational changes, so that the membrane permeability for ions is altered, resulting into important changes in metabolism.

For example insulin promotes the entry of glucose from blood into the muscles cells by increasing the permeability of sarcolemma to glucose.

Within a cell : The steroid hormones act within the Their small, lipid soluble molecules pass through the cell membrane and bind to specific receptor molecules present in the cytoplasm. The receptor molecules carry them into the nucleus. Here, the receptor hormone complex binds to a specific receptor site on the chromosome and activates certain genes that were previously repressed. The activated gene transcribe m-RNA which directs the synthesis of enzyme (protein molecule) in the cytoplasm. The enzyme molecule promote the metabolic reactions in the cell.
Feedback control of hormone secretion : The secretion of hormones is depends on age, daily routine, health of Physiological conditions of body etc. Besides the above factors hormone secretion is also depends on its own amount circulating in the blood. Decrease and increase in the circulating amount of a hormone

has a directly inverse effect on the secretion of hormone. This is known as the “pull and push” or “feed-back control” mechanism of hormonal secretion.

Several types of feedback mechanisms are found in the body. Most of these are of negative feedback, but some are of positive feedback. Some

HYPOTHALAMUS

negative feedback mechanisms are direct, while others are indirect.

(a) Negative feedback control

(1) Direct feedback control : Thyroid stimulating hormone (T.S.H.) stimulates the thyroid gland to secrete thyroxine hhormone. A high amount of thyroxine in the blood exerts an inhibitory effect on pituitory to secrete less T.S.H.. This eventually results a decrease in thyroxine. This is called “Direct feedback control”.

Thyroxine hormone : A high amount of thyroxine in the blood exerts an inhibitory effect correction. This eventually results a decrease in thyroxine. This is call “direct feedback control”.

Positive feedback control : Oxytocin released by posterior pituitary gland stimulate contraction of uterus during child As the

HIGH BLOOD LEVEL OF THYROXINE

LOW TRH

ANTERIOR PITUITARY

LOW TSH

HIGH TRH

HIGH TSH

LOW BLOOD LEVEL OF THYROXINE

contraction of uterus progresses, more and more of oxytocin is released. Thigh is called positive feed back control.

Origin of different endocrine glands

Fig. – Feed back control of hormone secretion

Endocrine glands	Weight	Origin
Pituitary	0.5 gm	Ectoderm
Pineal	5.0 mg	Ectoderm
Thymus (up to 12 yrs.)	20.0 gm	Mesoderm
Thyroid	25.0 gm	Endoderm
Parathyroid	20.0 mg	Endoderm
Adrenal cortex	4.0 gm	Mesoderm
Adrenal medulla	1.0 gm	Ectoderm
Testes	–	Mesoderm
Ovary	–	Mesoderm
Pancrease	60.0 gm	Endoderm

(2) Functions of some important hormones

MSH controls skin
Pituitary controls other endocrine
Thymosine secreted by the thymus gland provides immunity to the
Thyroid is the largest Its hormone thyroxine controls oxidative metabolism.
Normally, family planning pills consists of estrogen and progesterone.
The Leydig cells secrete
Steroid sex hormones are secreted by the The hormones control the process of reproduction and secondary sexual characters.
Adrenal gland is found attached to the kidney as This gland secretes adrenalin and non-adrenalin hormones.
Oxytocin controls
Prolactin controls growth is mammary glands and secretion of milk in
FSH controls
LH controls secretion of androgen from the Leydig cells in man and helps in the release of ovum from the ovary in

(3) Number of hormones secreted by different endocrine glands

Endocrine-glands	Number of secreted hormones
Pituitary – Anterior	–	7
Pituitary – Posterior	–	2
Pineal body	–	2
Thymus	–	3
Thyroid	–	2
Parathyroid	–	1
Islets of Langerhans	–	3
Adrenal cortex	–	46
Adrenal medulla	–	2
Testes	–	1
Ovary	–	3
Placenta	–	2
Kidneys	–	2
Stomach	–	1
Duodenum	–	5
Ileum	–	2

Discovery & Terms
Term ‘endocrine’ was first used by Bernard.
Thomas Addison is called as father of
Walter canon stated that the hormones maintain homeostasis in the
Von Euler coined the term ‘prostaglandin’
Kendall for the first time prepared the crystals of
Harrington and Barger studied the molecular structure of
Term ‘thyroxine’ was coned by Whartson.
Sutherland discovered
Parathormone was first isolated by
Potts discovered the structure of
Axelord studied the structure of epinephrin and nor-epinephrin.
Endocrine structures of the pancreas were discovered by
Structure of insulin was studied by Sanger. He was given Nobel prize in He was rewarded Nobel prize in 1980 for gene structure.
Human insulin was synthesized by Tsan.
Glucagon was discovered by Kimball and Murlin.
Term ‘ Secretin’ was coined by Beylis and Starling.
Adrenalin gland was discovered by Eustachian.

Pituitary Gland (Hypophysis)

Pituitory is known as hypophysis cerebri, its name pituitary was given by vesalius. Muller,s gland of amphioxus and subneural gland of hardmania is homologous to pituitary of vertebrates. Weight to pituitary is 0.5 gm. Removal of pituitary is knows as hypophysectomy.

Position and origin : Pituitary gland is the smallest (about 1 to 1½ cm in diameter) endocrine gland of the body. It is pea-shaped, ovoid, radish brown gland situated at the base of the brain in a cavity, the sell turcisa of sphenoid bone. It is connected by a short stalk called Infundibulum, to the ventral wall (Hypothalamus) of That is why it is also called hypophysis cerebri. It weight about 0.5 to 1 gm. It controls most of the endocrine glands. Hence, it is also called leader of endocrine orchestra or master gland. Pituitary gland is closely related with hypothalamus. Hence, it is also called hypothalamo-hypophyseal gland, pituitary is ectodermal in origin.

Parts and component

Adenohypophysis

Pars distalis
Pars tuberalis Anterior lobe
Pars intermedia

(2) Neurohypophysis

Pars nervosa

HYPOTHALAMUS

ANTERIOR PITUITARY

POSTERIOR PITUITARY

Infundibulum

Posterior lobe

Fig. – Location of pituitary gland

Structure of pituitary gland : Pituitary gland is comprised of two main lobes – Adenohypophysis and Adenohypophysis is arises as hypophysial or Rathke’s pouch from dorsal wall of embyronic stomodeum. It is the anterior lobe of pituitary. The neurohypophysis (Pars nervosa or Posterior lobe) form as an outgrowth from the infundibulum of the floor of hypothalamus.

The anterior lobe includes three lobes – Pars tuberalis, Pars distalis and pars intermedia. The posterior lobe includes pars nervosa and infundibulum. The pars nervosa has the axons of the neurosecretory cells found in the hypothalamus. The axons form end knows which are called as Herring bodies. There are special pituicytes in

between the Herring bodies which are called neuroglial cells.

HYPOTHALAMUS

PARS HYPOTHALAMUS TUBERALIS

3RD VENTRICLE

MEDIAN EMINENCE

MAMMILARY BODY

TUBER CINEREUM

MEDIAN EMINENCE

INFUNDIBULAR STEM

PARS NERVOSA

CLEFT

PARS TUBERALIS

PARS INTERMEDIA

PARS DISTALIS

INFUNDIBULAR STALK

PARS INTERMEDIA

PARS NERVOSA

POSTERIOR LOBE

ANTERIOR LOBE

PARS DISTALIS

Fig. – Structure of pituitary gland

In pituitary following types of cells are found –

(ANTERIOR LOBE)

Fig. – Gross structure of pituitary gland

Chromophase cells : Found in adenohypophysis of These are not stained by acid and base dye. Pigment granules are absent. These are colourless may change into chromophils.

Chromophil cells : Found in adenohypophysis of pituitary. These are stained by acid and base dye. Pigment granules are filled in these These may be two types –

Acidophils : It is also known as a-cells.
Basophils : It is also known as
- Pituecyte cells : These cells found in neurohypophysis of
- Herring bodies : These are the bodies which store

NEUROSECRETORY CELLS OF HYPOTHALAMUS

CAPILLARY BED HYPOTHALAMOHY-

POPHYSIAL PORTAL VEINS

SUPERIOR HYPOPHYSIAL ARTERY

ANTERIOR LOBE

HERING BODIES

AXON TERMINALS

Blood supply to pituitary : A pair of posterior hypophysial arteries and a pair of anterior hypophysial arteries provide blood to the

ADENOHYPOPHYSIS

INTERMEDIATE LOBE

PITUICYTES

VEIN NEUROHYPOPHYSIS

pituitary gland. Posterior arteries supply blood to the pars nervosa, and anterior arteries supply blood to the hypothalamus and pars distalis. Adenohypophysis has dual blood supply be means of a “circle of willis“. The anterior hypophysial artery which bring

blood into this circle bigureates in to two branches outside the lobe. One branch supplies the adenohypophysis and other supplies the hypothalamus. The veins that drain the blood from hypothalamus. Than run into the pars distalis through pars tuberalis and divide into capillaries. Those veins are therefore, called portal hypophysial veins. These constitute a hypothalamo – hypophysial portal system.

Hormones of adenohypophysis : Adenohypophysis secrets seven hormones which are proteinous in These hormones

PARAVENTICULAR NUCLEUS

SUPRAOPTIC NUCLEUS

MEDIAN EMINENCE

ANTERIOR PITUITARY

Fig. – Blood supply to pituitary

HYPOTHALAMUS

PORTAL SYSTEM INFUNDIBULUM

POSTERIOR PITUITRAY

KIDNEY TUBULES

MUSCLES OF UTERUS

controlled by the controlling factors. Secreted by the hypothalamus. These are 10 main controlling factors. Out of them 7 are releasing factor (RF) and 3 are inhibiting factor (IF). Complete failure of adenohypophysis (ant. pituitary) is leads to

simmonds syndroms. Various hormones of

MAMMARY GLAND

MUSCLE

FSH

ICSH LH

MELANOCYTES

ADRENAL CORTEX

adenohypophysis are as follows –

BONE TESTIS

OVARY

(a) Somatotropin (STH) or Growth Hormone (GH)

Fig. – Diagram to show the hormones of adenohypophysis and their target tissues and organs

Functions of growth hormone : Molecules of this hormone are polypeptides of 191 amino acid It is the major hormone in the secretion of anterior pituitary. It is the most important stimulant of proper normal growth of body. It promotes biosynthesis of DNA, RNA and proteins in all body cells. thus, it acts as an anabolic growth factor. Obviously, it stimulates cellular growth and proliferation, growth and repair of bones, muscles and connective tissue. In the liver cells it promotes, glycogenesis, deamination and gluconeogenesis. For production of energy (ATP) in cells, it retards utilization of glucose, and promotes mobilization of fat from adipose tissues for this purpose. The overall effect of growth hormone; is, thus, an increase in body proteins and carbohydrates reserve, but decrease in body fat.

According to modern scientists, the anabolic effects of growth hormone in man are indirect, instead of being direct. This hormone triggers synthesis of certain special, insulin-like growth factors (IGFs) in cells of many tissues, such as liver, muscles, cartilages, bones, etc. These growth factors are called somatomedins. These are secreted into blood, or act as local hormones in tissues. These promote protein systhesis in cells. Unlike insulin, these promote the use of fatty acids for energy and save glucose for fertilization by nerve cells even at times of fasting and hunger. Remember that African pigmys remain dwarf simply because somatomedins are not synthesized in their bodies.

Control of the secretion of growth hormone : Secretion of growth hormone is controlled by two hormonal factors secreted by cells of hypothalamus. One of these factors, called GH-release hormone (GHRH) promotes secretion of growth hormone, while the other called GH-inhibatory hormone (GHIH) retards the secretion of growth hormone by the anterior pituitary. GHRH is also called somatocrinin and GHIH is called somatostatin. Under negative feedback, amounts of glucose, fatty acids and amino acids in blood affect the secretion of GH by anterior pituitary increase in a few minutes. Conversely, increasing blood levels of glucose and fatty acids, or decreasing level of amino acid promote secretions of GHIH by hypothalamus which retards secretion of GH by anterior pituitary in minutes. After termination of growth period at about the age of 22 in adolescence, secretion of growth hormone starts decreasing with age, remaining only about 25% in old

(3) Effects of hyposecretion of growth hormone

Nanism or ateliosis : Hyposecretion (undersecretion) of growth hormone is childhood results into a blunted growth of Growth of all organs is retarded. Growth of bones at their epiphysial ends stops. Hence, the bones do not grow in length, so that the body remains a dwarf. This pituitary dwarfism is called nanism or ateliosis.

Growth of these dwarfs can be normalised if growth hormone is given as a drug to these from the beginning in childhood. Synthetic human growth hormone (hGH) is now being manufactured on commercial scale by DNA- recombinant technique.

Midgets : Unlike the thyroid cretinism, the development of brain is normal in pituitary dwarfs, but like thyroid cretinism, the pituitary dwarfs are also The dwarfs of circuses are pituitary dwarfs. these are called midgets.
Pituitary myxodema : Undersecretion of growth hormone during adolescence (between 13 to 22 years of age) restricts body height, so that the person remains short-statured. Undersecretion after growth period (about the age of 22) causes pituitary myxoedema whose symptoms are almost similar to those of thyroid These include old age symptoms, such as reduced BMR and protein synthesis, graying and falling of hair, pallor and dryness of skin, reduced BP and low body temperature, insomnia, and weakness of muscles, vision and wisdom. Due to accumulation of mucus under the skin, the body becomes puffy, but weak. Genitalia weaken, causing sexual debility. Hence, the person becomes disheartened.

(4) Effects of hypersecretion of growth hormone (N P)

Proportionate gignatism : Hypersecretion (oversecretion of growth hormone during growth period (childhood and adolescence) causes excessive growth (hypergrowth) of all body parts, resulting into a symmetrically giant This is called proportionate gigantism.
Disproportionate gignatism or acromegaly : The concerned person may attain a height of 8 feet or ever Oversecretion of growth hormone after growth period also causes gigantism, but in this the long bones do not grow in length due to closed hypophyses at their ends, but the bones of hands, feet, lower jaw and rib cage thicken. Simultaneoulsy, eyelids, lips, tongue, nose, chin, etc also enlarge. Soles, palms and forehead become wrinkled. Skin thickens and becomes wrinkled. Skin thickens and

HUNCHBACK

ACROMEGALIC FACE

HIRSUTIM

GYNECOMASTIA AND LACTATION

ENLARGED HANDS AND FEET

becomes coarse and fluffy (hirsutism). Consequently, the body becomes ugly like a gorilla. This is called disproportionate gigantism or acromegaly. It is common in men and rare in women.

Fig. – A typical case of acromegaly

Kyphosis : In some cases, the backbone bends and thickens, causing hunchback condition (kyphosis). Breasts enlarge and mammary gland may yield The patients often complain of headache, sexual disorders, muscular pain, and impaired vision and memory.
Diabetes mellitus : Hypersecretion of growth hormone raises blood glucose level (hyperglycemia) which may cause diabetes mellitus.
Ketosis : Increased breakdown of fat may release ketone bodies, mainly acetoacetic acid, in blood, causing

Prolactin (PRL), Lactogenic, Luteotropic (LTH), or Mammotropic (MTH) Hormone : It is secreted by the lactotroph cells of anterior pituitary. Its molecules are polypeptides of 198 amino acid monomers. Its secretion by anterior pituitary is enhanced by prolactin-release hormone (PRH) and suppressed by prolactin inhibitory hormone (PIH) of PIH is also called dopamine. In humans, it may act as a mild growth hormone, but its main physiological effect is to activate growth of breasts during pregnancy and secretion of milk by mammary glands after childbirth. That is why, it is often referred to as “maternity hormone“. In some other mammals, and probably in women also, it stimulates corpus luteum of ovaries to continue secreting progesterone hormone during pregnancy.
- Hypersecretion : Prolactin hormone is secreted both in males as well females in males it influence sexual Its hypersecretion may hinder menstruation.
- Hyposecretion : May cause In pigeons and doves, it stimulates the epithelial cells of crop in both and females to secrete “pigeon milk” for nutrition of newly hatched infants.
Follicle-stimulating hormone (FSH) or Gametokinetic factor : It is a glycoprotein whose molecules consists of a polypeptide of 204 amino acid It stimulates growth of seminiferous tubules and spermatogenesis in men, and growth of ovarian follicles and oogenesis in women. In women, it also stimulates secretion of female sex hormones (estrogens) by the cells of ovarian follicles. Under the negative feedback regulation, the principal male (testosterone) and female (estradiol) hormones retard secretion of FSH. In women,

the effect of FSH on ovaries considerably decreases after the age of 40. Consequently oogenesis, secretion of estrogens and mestruation decline and ultimately stop. Termination of mesntruation is called menopause.

Luteininzing hormone (LH), or Interstitial cell-stimulating hormone (ICSH) : This is also a glycoprotein whose molecules contain a polypeptide of 204 amino acid In men it stimulates the growth and function of the interstitial cells of testes (cells of Leydig), which secrete the male hormones (androgens) to regulate the development of secondary sexual characteristics. In women, it stimulates the last stages of oogenesis, ovulation, development of corpus luteum and secretion of progesterone by the corpus luteum.

Both FSH and LH are secreted by the gonadotroph cells of anterior pituitary. Since both of these stimulate growth and activities of gonads, these are called gonadotropic hormones. These also activities the accessory genital organs. Secretion of these hormones begins only two to three years before puberty (age of sexual maturity – 12 to 14 years). Obviously their secretion is initiated by a “Genetic biological clock”, located in hypothalamus. Further, the secretion of FSH in women is also regulated by a “Clock”, located hypothalamus. Further, the secretion of FSH in women is also regulated by a “Clock of menstrual cycle”. Under the regulation of both these clocks a gonadotropin- release hormone (GnRH) is secreted by hypothalamus and influences the activities of pituitary gonadotroph cells. Synthetic hormones of this category and their antegonists are now used to respectively activate or retard the activities of gonads.

Adrenocorticotropin or Adrenocorticotropic hormone (ACTH) : It is secreted by corticotroph cells of anterior Its molecules are 39 amino acid polypeptides. Its secretion or prompted by a corticotropin- release hormone (CRH) of hypothalamus. Its role is to intensity synthesis of adrenal cortical hormones, particularly the glucocorticoids. Secretion of ACTH is stimulated by low blood level of glucose, shock conditions and presence of a compound called interleukin-1 (IL-1) secreted by macrophages. Under a direct negative feedback regulation, the concentrations of glucocorticoids in blood affect the secretion of both ACTH and CRH. Hyposecretion of ACTH leads to rheumatic arthritis.
Thyrotropin or Thyroid-stimulating hormone (TSH) : It is also a glycoprotein secreted by thyrotroph cells of anterior pituitary. The polypeptide of its molecule has 201 amino acid residues. Its secretion is stimulated by a hypothalamic thyrotropin-release hormone (TRH). It promotes growth and function of thyroid Under the negative feedback regulation, the secretion rate of hypothalamic TRH depends on blood levels of TSH, thyroxine and glucose, and on metabolic rates of body cells.
Melanocyte-stimulating hormone (MSH) or Melanotropin : It was formerly called intermedin secreted by pars intermedia. This may be the condition in other vertebrates, but in humans, it is secreted by remmant cells of this lobe, which become a part of pars distalis. Its molecule is a small peptide of 13 amino acid Its secretion is controlled by two hypothalamic hormones, viz MSH-release hormone (MSHRH) and MSH- inhibitory hormone (MSHIH). In lower vertebrates, the target cells of this hormone are the melanophores melanin is antagonistic to melanocyte stimulating hormone affects spreading of the melanin granules in these cells so that skin colour derkens in fish and amphibian but in birds and mammals of the role of MSH in uncertain. In man, it is probably responsible for bronzing of skin, moles and freckles.
Metabolic hormone (MH) : It influence carbohydrate and fat metabolism of The hormone which influence carbohydrate metabolism is known as diabetogenic hormone. The hormone which influence fat metabolism is known as ketogenic hormone.

(v) Hormones of neurohypophysis and their functions : The hering bodies of neurohypophysis contain two hormones – vasopressin and oxytocin – which are released from axon terminals by exocytosis and diffuse into adjacent blood capillaries when needed. These are secreted by paraventricular nucleus and supra-optic nucleus respectively both vasopressin and oxytocin are protenous in nature.

Vasopressin : The principal role of this hormone is to promote reabsorption of water from the distal convoluted tubules of nephrons and collecting ducts reducing excretion of water in urine (diuresis). That is why, it is also called antidiuretic hormone (ADH). Its release into blood is controlled by as “osmoregulatory centre” located in Another effect of vasopressin is to increase blood pressure by contracting blood vessels (vasoconstriction) in several tissues; hence the name vasopressin.

Effect of vasopressin

Vasoconstriction of the blood vessels of skin by this hormone retards secretion of sweat glands.
It also stimulates contraction of intestinal smooth
When vasopressin is released in excessive amounts, the urine becomes concentrated and blood is diluted, increasing The osmo-regulatory centre, then, issues motor impulses to check release of vasopressin.
When vasopressin is released in smaller amounts, diuresis increases; urine becomes diluted and blood becomes concentrate, amounts, diuresis increase; urine becomes diluted and blood becomes concentrated, decreasing
In acute diuresis, quantity of urine may increase to about 20 litres instead of normal 1 to 2 litres per This condition is called polyurea or diabetes insipidus (passing of water; tasteless urine). It causes dehydration of body and thirst.

Patients may die soon if water is not available. Synthetic ADH, called pitressin is used for antidiuresis.

Under the control of hypothalamic osmo-regulatory centre, secretion of ADH increases with increase is osmotic pressure in ECF, and decreases with decrease in osmotic pressure in ECF. Contrarily, drinking of tea, coffee and wine, decreases ADH secretion, causing diuresis and dehydration. That is why, one feels thirsty after drinking wine and suffers from headache the next morning. This is called hangover.

ADH is also secreted more in kangaru rat (Dipodomys). Kangaru rat never drink water throughout the life. ADH is secreted less in alcoholic condition. Patient feel thirsty, dehydration may appear and RBC count and protein in blood increases. ADH secretion increases in stress and emotional conditions.

Thy oxytocin (Child birth hormone) : This hormone stimulates contraction of uterine muscles, inducing labour pains for child birth (parturition) when secretion of progesterone hormone from the placenta declines, making the end of As the sensory impulse of increasing labour pain reaches hypothalamus, more and more oxytocin is released from posterior pituitary under a positive feedback regulation. Possibly oxytocin is released at this time by posterior pituitary of both mother and the fetus. At actual childbirth, it dilates the cervix (vaginal stretching). After childbirth, it helps in normalization of the uterus and contracts breast muscles and lactic ducts to facilitate release of milk (lactation) during sucking oxytocin stimulates milk ejection so has a galactogogic effect. Remember, the milkmen inject synthetic oxytocin, called pitocin, into their cows and she buffaloes to get more milk. Release of oxytocin increases in women during coitus for intensifying uterine contractions, so that male’s semen may easily ascend along the fallopian tubes to facilitate fertilization of ova. Role of oxytocin in men and nonpregnant women is unknown. Possibly, it increases affection for children and passion and pleasure during coitus.

Master gland : As is clear from above account, the pituitary gland plays most important regulatory role in the body. Besides regulating growth, sex and general behaviour, it also regulates the secretory activities of other principal endocrine glands and cells. Most appropriately, therefore, pituitary has been referred to as “The Master Gland” of body, or the “Chief Executive of Endocrine System”, or “The Leader of Endocrine Orchestra”.

Hypothalamus

Position and Structure : Hypothalamus is the floor of diencephalon. It is formed of masses of grey matter, called hypothalmic nuclei, containing neurosecretory It is connected with anterior pituitary lobe by blood capillaries of hypophyseal portal system and with the posterior pituitary lobe by axons of its neurons, both passing through the pituitary stalk.
Hormones of hypothalamus : Neurosecretory cells of hypothalamus secrete neurohormones called releasing factors (RF) or inhibiting factors (IF). These neurohormones are carried by hypophyseal portal system to adenohypophysis (primary target organ) and stimulate or inhibit the release of trophic hormones from These neurohormones are proteinous in nature and formed of 3 – 20 amino acids.

Neurohormones of Adenohypophysis

Neurohormones	Physiological effects
(1) TSH-RF
(Thyroid Stimulating Hormone – Releasing Factor)	Increased ACTH secretion from adenohypophysis.
(2) ACTH-RF
(Adrenocorticotrophic Hormone-Releasing Factor)	Increased ACTH secretion from adenohypophysis.
(3) STH-RF
(Somatotrophic Hormone-Releasing Factor)	Increased STH secretion from adenohypophysis
(4) SOMATOSTATIN (GROWTH INHIBITING HORMONE)	Decreased STH secretion from adenohypophysis.
(5) GTH-RF
(Gonadotrophic Hormone-Releasing Factor)
(i) FSH-RF
(Follicular Stimulating Hormone-Releasing Factor)	Increased FSH secretion from adenohypophysis.
(ii) LH-RH (In female)
(Luteinising Hormone – Releasing Factor)	Increased LH secretion from adenohypophysis.
or ICSH-RF (In male)
(Interstitial Cells stimulating Hormone-Releasing Factor)
(6) Prolactin-Releasing hormone (P-RH)	Increased secretion of prolactin or leutotrophic hormone.
(7) Prolactin-Inhibiting hormone (P-IH)	Increased secretion of prolactin or leutotrophic hormone.
(8) MSH-RF
(Melanophore Stimulating Hormone-Releasing Factor)	Increased MSH secretion from intermediate pituitary lobe.
(9) MIF
(Melanophore Inhibiting Factor)	Decreased MSH secretion from intermediate pituitary lobe.

Hypothalamo – pituitary complex : Pituitary gland is closely related with Both together form hypothalamo-pituitary complex.

The hypothalmic-pituitary (hypothalamo-hypophyseal) system is a direct proof of coordination between the hormonal and nervous system. It regulates most of the physiological activities of body and maintains homeostasis inside the body. These neurosecretory cells are known to synthesize two more hormones : Oxytocin and Vasopressin, which are stored in their axons extending in the posterior lobe of pituitary gland.

Important tips

The word ‘endocrine’ derives from a Greek word meaning ‘I separate within’.
‘Chemical messengers’ called the
Huxlex called hormones as ‘chemical messengers’. Hormones are also known as ‘autocoids’.
The word ‘hormone’ is derived from a Greek work meaning ‘I excite or ‘
The work ‘hormone’ was first used in reference to secretin and
The father of endocrinolgy is Thomas The first endocrine disease reported was Addison’s disease (1855) caused by the destruction of adrenal cortex.
Pancreas is a mixed gland (heterocrine), with exocrine and endocrine
When some hormones work together to control a process, this is called synergism, g., FSH and LH.
When two hormones work against each other to control a process, this is called antagonism, g., Insulin and Glucagon, Calcitonin and Parathormone.
There are some hormone – like substances, but not the products of endocrine They are parahormones, e.g., Prostaglandins and Pheromones.
Hormones are not present in food but are synthesized in
Protein hormones act at membrane level and change the permeability of plasma
Steroid hormones enter nucleus and inavtivate or activate the function of some
Although thyroxine is not a steroid hormone but it is lipid soluble and acts as gene level like steroid
Water soluble hormones act through extracellular
Lipid soluble hormones act through intracellular
Insulin receptor is a heterotetrameric protein consisting of 2a subunits and two b
One signaling molecules activates many mediators and one molecule of mediator activates hundreds of other
In this way a signal is amplified hundred
Insulin activates ® about 100 molecules of protein kinase A (about 100 molecules of enzyme phosphorylase kinase).
Pituitary gland is called “Master gland” or “The leader of Endocrine Orchestra”.
All hormones of anterior pituitary control secretion of other endocrine glands except for somatotrophic hormone which is directly responsible for the growth of
Secretion of hormones is regulated by feed back control
Hormones secreted at nerve endings are called neurochoromones or
Sutherland received Noble prize in 1971 for his contribution in field of understanding of mechanism of hormone
Secondary messengers are intermediate compounds that amplify a hormonal
Due to amplification of signals single molecule of adrenaline may lead to release of about 100 million molecules of
Amplification of signals is the reason why small amount of hormones can trigger many metabolic
Heart muscles use cAMP as secondary messenger for adrenaline and cGMP as secondary messenger for
By using two opposite signals within a cell sympathetic and parasympathetic nervous system achieve opposite

Cells have receptors for insulin and glucagons which also have antagonistic
Although thyroxine is not a steroid hormone but it is lipid soluble and acts at gene level like steroid
Action of protein hormones is faster and not long
Action of steroid hormones is slow, wide spread and long
The level of hormones in our blood can be measured by radio immuno assay (RIA).
Endocrine glands with ducts are pancreas, ovaries and
Primary targate organ of hypothalamus is pituitary
In amphibious and reptiles pineal gland is considered third vestigeal
In human pituitary, the intermediate lobe is functional in embryo but is rudimentary in
One neuron-one hormone hypothesis is followed by
Growth hormone is the only hormone of anterior pituitary that has direct effect on body
Median eminance is a part of post
Myosisthemia gravis : Abnormal neuromuscular excitation due to hypersecretion of
Histologically, pituitary gland is formed of 5 types of endocrine cells : Somatotropes : 30 to 40% and secrete growth hormone or Corticotropes : About 20% and secrete ACTH.

Thyrotropes : Secrete TSH

Lactotropes : Secrete prolactin

Gonadotropes : Secrete FSH and LH in female, and FSH and ICSH in male.

Hormones are also called autocoids or chemical messengers or information
Local hormones are also called para-hormones or tissue
First discovered hormone was secretin but first isolated hormone was insulin and was isolated from pancreas of dogs by Banting and
Thyroxine hormone is derived from tyrosine amino acid while oxytocin and ADH ar short chain peptide
Pheromones : These are intra-specific chemical messengers released by an animal into air to initiate specific response in another animal of same species. These may be signals of food, mate etc. These are also called ectohormones. Term pheromone was coined by Karlson and Butenandt (1959).
Feedback inhibition : In this, end product sends certain inhibatory signals (called negative feedback) when end product is at required
Endocrinologist : Scientist involved in the study of endocrine
Ecdysone : A steroid hormone secreted by prothoracic glands present in the prothorax of insects the cockroach and controls moulting or
Corpora cardiaca : A part of rod-like endocrine glands found in insects on the sides of oesophagas and secrete growth hormone which controls the growth of
Juvenile hormone : Secreted by a pair of rounded endocrine glands called corpora allata, present just behind corpora These secrete juvenile hormone in the nymphal stage and checks the appearance of adult characters.
Baldness in human beings is a sex-influenced It is more common in males as the autosomal gene of baldness acts as dominant in the presence of testosterone (male hormone) but acts as recessive in the presence of oestrogens (female hormones).
Level of hormones in our blood can be measured by Radio Immune Assay (RIA).
Hormone receptors are always proteinous and are located either on cell membrane of target cells or in
Spleen does not secrete any
Basal metabolic rate (BMR) – minimum energy required during rest or sleep (160 Kcal/day).
Thyroid gland is only endocrine gland that stores its secretory

Thyroid gland

The name “thyroid” was introduced by Thomas Wharton (1656). It is derived from Greek “Thyreos” a shield.

Location : This is the largest endocrine gland of our body. It is located in our neck upon the ventral aspect of larynx (sound box or Adam’s apple) and a few anteriomost tracheal rings. It is a dark brown and H-shaped bilobed
Origin : It is endodermal in origin and arises in the embryo as a midventral process from the floor of the tongue in pharyngeal region between the first and second pharyngeal pouches. Later, the duct-like connection (thyroglossal duct) of the process degenerates, so that the process is separated from the tongue and becomes Probably, the gland is homologous to the endostyle of lower chordates.
Structure of thyroid gland : In adult human

beings, thyroid gland measures about 5 cm in length and 3 cm in width. It’s average weight is 25 grams. It is somewhat larger in women. In old age, it becomes somewhat smaller as age advances. Its two lobes are connected by a narrower isthmus formed of nonglandular connective tissue. A small, conical pyramidal lobe is often found extended forwards from the isthmus. The whole gland is

enveloped by a fibrous capsule. Thin septa or trabeculae,

PARATHYROID

PYRAMIDAL LOBE

THYROID

ISTHMUS

BLOOD CAPILLARY

LARYNX

THYROID FOLLICLES

IODOTHYRO- GLOBULIN

extending inwards from the capsule, divide the gland into a number of lobules. Each lobule, in turn, consists of a large number of small and hollow, spherical follicles (acini) embedded in a small amount of a loose connective tissue that forms the stroma of the gland.

‘C’ CELLS

TRACHEA STROMA

Fig. – (A) Thyroid gland,

Follicles suspended in stroma of a lobule

The wall of each thyroid consists of a single-layered cuboidal epithelium suspended from a basal lamina, while its cavity is filled with a yellowish, jelly-like and iodinated colloid glycoprotein substance, called iodothyroglobulin. Besides containing a dense network of blood capillaries, the stroma contains small clusters of specialized parafollicular or ‘C’ cells. The latter are remnants of ultimobranchial bodies derived from the fifth pharyngeal (branchial) pouches in the embryo.

Synthesis and storage of iodothyroglobulin : Synthesis of a glycoprotein thyroglobulin (TGB) – occurs continuosly in the follicular cells under genic control. The cells keep extruding thyroglobulin in follicular cavity by excytosis. Each molecule of thyroglobulin contains about 500 amino acid momoners of which 123 monomers are of tyrosine at fixed Soon as the molecules of iodine and thyroglobulin come out of follicular cells, these interact in such a way that 15 tyrosine monomers of each thyroglubulin molecule at fixed places become iodinated. Certain tyrosine monomers bind with single atoms of iodine, formine monoiodotyrosine (MIT or T₁). Other tyrosine monomers bind with two atoms of iodine, forming diiodotyrosine (DIT or T₂). This is called organification of thyroglobulin. Molecules of iodothyroglobulin keep accumulating in follicular cavity, forming the

jelly-like colloid. Within the collodi, molecules of iodothyroglobulin undergo conformational changes and may even interact with each other. This results in a coupling of most of the iodinated tyrosine monomers in pairs. This coupling may occur between the iodinated tyrosine monomers in pairs. This coupling may occur between the iodinated tyrosine monomers of the same or different molecules of iodothyroglobulin. It results in the formation of several groups of complexes of tetraiodothyronine (thyroxine – T₄) and some of triiodothyronine (T₃) in the colloid. Each T₄ complex obviously contains two throsine monomers and four atoms of iodine, whereas each triiodothyronine complex contain two tyrosine monomers and three atoms of iodine. T₄ and T₃ are actually the iodinated hormones secreted by thyroid. Obviously, the colloid acts as a reservoir of these hormones.

E.C. Kendall (1914) was the first to obtain thyroxine in pure form and to coin its name. Later, Harrington and Barger (1927) worked out its molecular structure.

Lysosomes fuse with these vesicles and their enzymes hydrolyze the molecules of iodothyroglobulin. Consequently, T₄ and T₃ become free and, being lipid-soluble, these diffuse through the plasma membrane into ECF and thence, into the blood. In blood, most of the T₄ and T₃ molecules bind with molecules of a transport protein different binding protein named thyroxine-binding prealbumin (TBPA).

The daily output of thyroid glands is about 80mg (0.08mg) of T₄ and about 4mg of T₃. Since, however T₃ is several times more potent, most of the T₄ molecules also change into T₃ molecules by losing one iodine atom as these diffuse from blood into ECF. This deiodination of T₄ is maximum in the liver.

As described in a preceding account, the rate of thyroid secretion is controlled by pituitary gland and the hypothalamus of brain respectively under direct and indirect negative feedback regulation. Rate of thyroid secretion increases during winters and in pregnant women.

(v) Synthesis and secretion of iodinated hormones

Iodides and Iodine : An adult human body contains about 5 to 6 milligram of iodine and most of it is found in thyroid gland. Thus, the thyroid is a reservoir or iodine. For secreting the iodinated hormones in normal amounts, the thyroid daily utilizes about 150 micrograms (0.15 milligram) of iodine. Obviously, a person must daily obtain 150mg of iodine from food. We can obtain this from diary products, drinking water, seafood, etc. If obtained

more than this, we excrete the excess iodine in urine.

Iodine of food is absorbed and circulated in blood in the form of iodide ions (I^–). Follicular cells of thyroid very actively obtain these ions from blood by active transport. That is why, the concentration of I^– in these cells normally remains about 50 to 250 times more than in blood. These cells possess peroxidase enzyme in abundance. Perosicase continuosly oxidizes iodide ions into molecular iodine (2I^–

®I₂). Iodine is, then, released by follicular cells into follicular cavity.

BLOOD CAPILLARY

I–

I– I–

T₃

BASAL LAMINA

I–

I– PEROXIDASE

I– I₂

NUCLEUS

T₃

EXOCYTOSIS OF THYROGLOBULIN

LOBOTHYRO- GLOBULIN

Hormones of thyroid : Thyroid gland secretes two iodinated hormones. Thyroxine and Thyrocalcitonin (TCT) and one non iodinated hormone thyrocalcitonin. Secretion of thyroid gland is regulated by TSH of anterior

T4 T4

HYDROLYSIS

LYSOSOME

ENDOCYTOSIS OF IODOTHYROGLOBULIN

pituitary lobe. Thyroxine was first isolated by Kandall (1914) but was first crystalized by Kendall (1919). Its molecular structure was given by Harrington and Berger (1927).

Fig. – Working mechanism of follicular cells of thyroid

Thyroxine : It is an iodine containing (6% iodine) amine hormone which is derived from tyrosine amino Chemically thyroxine is tetraidothyronine though also found as tri-iodothyronine. Secretion of thyroxine is inversely proportional to the blood level of thyroxine (feed back mechanism). These hormones perform following functions :

These regulate Basal Metabolic Rate (BMR) of the body as control rate of cell respiration and energy production in mitochondria hence the “Temp. of life”. So these control physical, mental and sexual growth of It is called calorigenic effect.

Enhancement of BMR by these hormones results in an increase in protein synthesis in cells, rate of heartbeat, food absorption in intestine, glycogenesis, deamination and gluconeogenesis in liver cells, synthesis and actions of other hormones, conversion of carotene to vitamin A in liver cells, and many other processes. These hormones also increase irritability and regulate cholesterol level in blood. Considering all these effects in totality, these hormones are necessary for healthy life and growth and development of body.

In 1912 Gudernatsch discovered that metamorphosis in frog’s tadpole begins only when adequate amount of thyroxine is secreted by the thyroid of the tadpole. It was also found that hyposecretion of thyroxine retards and hypersecretion enhances the rate of

In the hilly tracts of North America from whose soil all iodine has been washed away by rain water, the tadpoles of Ambystoma probably never metamorphose. Therefore, these tadpoles grow to a large size and attain sexual maturity, i.e. these become paedogenetic larvae. This phenomenon is called neoteny. The neotenic larvae of Ambystoma are called Axolotl larvae.

Addition of thyroxine or iodine is pond water naturally induces and enhances metamorphosis in the tadpoles.

Functions of osmo-regulation and regulation of moulting have been ascribed to these thyroid hormones in cold-blooded vertebrates (fishes, amphibians and reptiles).
These control working by renal tubules of kidney so control urine
These help in homeothermy in warm blooded

Thyrocalcitonin (TCT) : It is a long peptide hormone secreted by parafollicular by cells of thyroid gland (C-cells). It secretion is regulated by increased plasma level of calcium by feedback mechanism. TCT lower calcinum level in blood to normal by :

Increasing calcium deposition in the bones, so checks osteoporosis and stimulates excretion of calcium in urine. Its prevent hypercalcaemia. Decreasing reabsorption of calcium from urine, so increasing excretion of Ca²⁺. So it prevent hypercalcaemia.

(vii) Irregularities of thyroid gland

Hypothyroidism : (Decreased section of thyroxine from thyroid gland). It leads to the following diseases :
- Cretirusm : It is disease of infants, called certin. It is characterised by Decreased BMR (50% than normal); stunted growth; retarded mental development so low Q., delayed puberty; decreased body temperature, heart rate, pulse rate, blood pressure and cardiac output; reduced urine output; decreased sugar level in blood, pigeon’s chest (chest bulging forward in sternal region). Cretinism can be congenital (absence of thyroid due to genetic defect) of indemic (absence of iodine in diet). It can be corrected by thyromin administration.
- Myxoedema : It occurs due to deficiency of thyroxine in adults like certinism, it also has low (BMR) (by 30 – 40%); low body temperature, reduced heart rate, pulse rate, blood pressure and cardiac output, low sugar and iodine level in blood etc. But the peculiar feature of myxoedema is that face and hands become swollen due to deposition of albuminous myxomatous It can also be corrected by thyroxine administration.

Endemic or simple goitre or colloid goitre : It occurs due to deficiency of iodine in drinking It is non-genetic (sporadic goitre is a genetic disease). It is characterized by enlargement of thyroid gland due to increase in number and size of acinal cells of thyroid gland. It is more common in people of hilly region. To prevent goitre, the table salt is being iodised these days.
Hashimoto’s disease : It is called auto-immune thyroiditis and occurs due to age factor, injury-surgery, wrong treatment or injection thyroid gland causing hyposecretion of thyroxine. When thyroxine secretion falls upto minimal limit, the antibodies are formed which destroy the thyroid

Hypersecretion of thyroid hormones (Hyperthyroidism or thyrotoxicosis) : This may also be a genetic defect, but usually it is provided by chronic infections (influenza, rheumatism, tonsilitis, tuberculosis, measles, whooping cough, etc.) pregnancy, intake of large doses of iodine, over-eating, etc. It results into a considerable increase in glucose and oxygen consumption by cells and the rate of oxidative metabolism in the Consequently, the BMR (basal metabolic rate) may increase severalfolds (hypermetabolism). The cells fail to store all catabolic energy into ATP. Consequently, the extra energy is liberated as heat. Instead of causing growth of body, this energy, thus, overheats the body, causing nervous tension and excitement, restlessness and anxiety, muscular weakness (thyrotoxic myopathy), fatigue and tremors, high temperature, palpitation of heart, copious sweating, diarrhoea, insomania, trembling of limbs and body, weight loss, heat intolerance, warm and soft skin, increased appetite, etc.

Under his “Sodium pump theory of thermogenesis”. Edelman has recently (1974) hypothesized that overheating of body in hyperthyroidism is not because cells fail to trap the excess catabolic energy in ATP, but because the excess ATP formed in this condition is utilized in considerably accelerating the Na⁺–K⁺ pump, relesing more heat that overheats the body.

Goitre : Hyperthyroidism may be simply because of overactive cells of a normal gland, or because of an enlargement of the gland, causing
Exophthalmic goitre : Such a goitre is called exophthalmic goitre, because it is usually accompanied with some asymmetrical protrusion (Exophthalmos) of the eyeballs, imparting an angry, frightened, or staring look to the Protrusion of eyeballs is due to accumulation of mucus in eye orbits.
Grave;s or Basedow’s disease : Enlargement of the gland is usually due to a diffused growth.

(4) Plummer’s disease or Toxic Adenoma : It is

due to formation of one or more hypersecretoy nodules Plummer’s disease or Toxic Adenoma in the gland.

Thyrocalcitonin (Calcitonin) : This is a noniodinized hormone secreted by the parafollicular cells (clear or C cells) of thyroid stroma. It retards bone dissolution and stimulates excretion of calcium in urine.

THYROID FOLLICLES

PARATHYROID

BLOOD CAPILLARY

CHIEF CELLS

Thus, it lowers calcium level in ECF. Its role is discussed with the role of parathyroid hormone.

CAPSULE OF THYROID

CAPSULE OXYPHIL CELLS

(B)

Parathyroid gland

Fig. – (A) Parathyroid gland embedded in the surface of thyroid, (B) Ultrastructure of a parathyroid

Position and structure : These are four in number which are wholly are partially embedded in the dorsal surface of the thyroid gland two glands in each lobe of thyroid Each is oval shaped, small sized (5´5 mm)

and yellow coloured. Histologically, a parathyroid gland is formed of masses of polygonal cell arranged in cords. Endocrine cell are two types principal or chief and oxyphil cells. Parathyroid is endodermal in origin.

Hormones of parathyroid : Active hormone secreted by parathyroids is parathormone (PTH), also called Collip’s Hormone (Phillips collip, 1925). It was discovered and purified by Collip in Its crystals wave first prepared by Craig and Ras mussen in 1960. Its molecular structure was worked out by potts and his associates in 1971. The latter is a protein of 84 amino acid monomer. It is a polypeptide hormone. Parathyroids are present in all vertebrates except fishes. Its secretion is stimulated by low level of calcium in blood than normal level through feedback control.

Functions of parathormone : Parathormone is essential for survival, because it significantly contributes to “homeostatis” by regulating the amount of calcium and phosphate ions in ECF. Our body requires an optimum calcium level (10.0 to 11.5 mg per 100mL.) in ECF (total 1000 to 1120 grams in a 70 kg man), because calcium is a key element in many physiological functions like proper permeability of cell membranes, muscular activities, nerve impulse conduction, heartbeat, blood coagulation, bone formation, fertilization of ova, etc. Calcium is most abundant of all minerals found in the body and about 99% of calcium and phosphorous are contained in the bones.

Maintenance of proper calcium level under ‘homeostasis’ is, in fact, a combined function of parathormone, thyrocalcitonin and vitamin D₃ (cholecalciferol). Parathormone promotes absorption of calcium from food in the intestine and its reabsoption from nephrons in the kidneys. Simultaneously, it accelerates elimination of phosphates in urine (phosphaturic action). Thus, calcium level tends to rise in the ECF due to the effect of parathormone. This calcium is, then, utilized by bone-forming cells – osteoblast – in bone formation under the influence of vitamin D₃. Bones are asymmetrical when first formed. Their unnecessary parts are, therefore, dissolved by bone-eating cells called osteoclasts. This process also proceeds under the influence of parathormone. It results in release of calcium and phosphate in blood.

The above process of bone-remodelling or reshaping, i.e. laying of new bone (by stimulating osteoblast activity), and dissolution of asymmetrical parts of newly laid bones (by stimulating osteoclast activity) continues in the body throughout life under the influence of vitamin D₃ and parathormone to serve as a mechanism of Ca²⁺ homeostatis. Role of vitamin D₃ and parathormone in this process is obviously synergetic. Contrary to this, thyrocalcitonin of thyroid gland retards bone dissolution and accelerates excretion of calcium in urine. Its role is, thus, antagonistic to that of parathormone. In healthy people, parathormone and thyrocalcitonin are, therefore, in a state dynamic equilibrium.

Vitamin D₃, is a steroid hormone which is first synthesized in an inactive form in skin cells from 7- dehydrocholesterol under the influence of ultraviolet (UV) rays of sunlight. Skin cells release it in blood. Liver cells take it from blood, change in into 25-hydroxycholecalciferol and release back into blood. Finally, the cells of proximal convoluted tubules of nephrons in the kidneys change 25-hydroxycholecalciferol into 1-25- dihydroxycholecalciferol under the influence of parathormone. This last compound is released in blood as active vitamin D₃ named as cholecalciferol (calcitriol).

In addition to its role in bone-remodelling, D₃ also stimulates absorption of Ca²⁺ and Mg²⁺ in intestine. Similarly, parathormone also plays an additional role of stimulating excretion of Na⁺, K⁺ and HCO^–₃, but retarding the excretion of Mg²⁺.

(iii) Irregularities of parathormones

Hypoparathyroidism (Hyposecretion of parathormone)

It is rare, However, in undersecretion of parathormone, the level of calcium in ECF falls (hypocalcemia), and that of phosphates rises (hyperphosphatemia). This causes neuromuscular hyperexcitability, excessive perspiration, gooseflesh (raising of hairs and prickly sensation in skin), cooling of hands and feet, painful muscular spasms and convulsions, and
Sometimes some skeletal muscles, usually of hands and feet, fail to relax after a contraction, and remain in “sustained contraction”. This is called “Tetany“. Tetany of larygneal, thoracic, and phrenic muscles, which help in breathing, causes death, because the patient fails to breathe (asphyxia).
Childhood hypoparthyroidism retards growth, particularly of bones, teeth, hair and brain. Vitamin D is administered to such

(b) Hyperparathyroidism (Hypersecretion of parathormone) :

Osteoporosis : Oversecretion of parathormone is rare and occurs usually due to overgrowth of one or more parathyroid glands. It causes demineralization bones which, therefore, become soft, weak, distorted and This is called osteoporosis.
Hypercalcemia : Simultaneously, due to a sharp rise in calcium level in blood and ECF (hypercalcemia) and a sharp fall in phosphate level (hypophosphatemia), muscles and nerves are
Hypercalciurea : Calcium is excreted in urine (hypercalciurea), thirst increases owing to copius urination, appetite is lost, constipation and headache become common, and often, kidney stones are formed. The only treatment so far known is removal of extra part of the glands by

Feedback control of secretion of parathormone and thyrocalcitonin : Secretion of these two hormones is continuously regulated by a direct negative feedback. As Ca²⁺ levels tends to fall, secretion of parathormone increases, but that of thyrocalcitonin decreases. Contrarily, the secretion of parathormone decreases and that of thyrocalcitonin increases when Ca²⁺ level tends to rise in blood.

Adrenal gland

Adrenal gland was first reported by Eustachius.

Origin and position : The adrenals are paired glands placed on the top of the kidneys as cap. Hence, they are also called suprarenal glands.

Adrenals have a dual origin, they are originated from ectoderm and mesoderm both.

Structure : Each adrenal is a small ( 5 cm long, 3 cm broad and 1 cm thick), triangular and yellowish cap like Its weight in humans is

MEDULLA

CORTEX (70%

TO 75%) ADRENAL GLAND

about 4 to 6 gm. Each gland has two parts – Outer cortex and inner medulla.

Outer cortex : The cortex is derived from mesoderm and forms about 80% part of the gland. Outside the cortex a thin connective tissue capsule is Cortex consists of fatty, cholesterol rich cells. These cells distinguish the cortex into three zones or regions.
- Zona glomerulosa : It is the outer part of the cortex (15% of the

(25% TO 30%)

KIDNEY

URETER

gland), which consists of small polyhedral cells. It secrets mineralocorticoids

e.g. Aldosterone.

Fig. – Adrenal gland with a part cut to show cortex and medulla

Zona fasciculata : It is the middle part of the cortex (50% of the gland). Which consists of large polyhedral This part secrets gluco-corticoids. e.g. Cartison, carticosterone.

Zona Reticularis : It is the inner part of the cortex (7% of the gland). In which the parallel cell cords of the zona fasciculata branched to form a loose anastomasing It secrets sex hormones.

Inner medulla : The medulla is derived from ectoderm and forms about 20% part of the Adrenal medulla is reddish brown in colour and colourless of rounded groups of short cords of relatively large and granular cells. These cells are modified postganglionic cells of sympathetic nervous system. These are called chromaffin cells or phaeochromocytes. Adrenal medulla secrets adrenalin and nor-adrenalin which are collectively called as catecholamines.
- Hormones of adrenal cortex : Abut 20 steroids (steriodogenic) compounds have secreted from adrenal These are called adrenocorticoids (cortiosteroids). Only few of them are biologically active as hormone. these hormones or steroid in nature. The letter, however account about 80% of the secretion of adrenal cortex and are classified in to three categories.

Mineralo-corticoids : The principal mineralocorticoid is aldosterone. It is also called salt-retaining hormone. It promotes reabsorption of sodium ions from kidney and excretion of potassium ions in urin. It also reabsorb Cl^– ions from kidney. Thus aldosterone has a important contribution in homeostasis by controling osmatic pressure of ECF (Extra cellular fluid).

Remember that doctors administer saline drip to the patients who lose excessive water and salts due to diarrhoea, cholera, etc. Aldosterone

also helps in maintaining acid-base equilibrium and blood pH (7.35) by

NERVE

BLOOD VESSEL

CAPILLARY

COLUMN OF PALE CELLS

CAPSULE

ZONA GLOMERULOSA (ALDOSTERONE)

ZONA

– + FASCICULATA

promoting reabsorption of HCO ₃ and regulating excretion of H

by (CORTISO)

kidneys. It also promotes absorption of water and salt in intestine, mainly in colon.

Gluco-corticoids : These include two main hormones – cortisol and carsicasterone. Cartisol is most abundant (about 95%) and most These hormones play an important role in carbodydrate, fat and protein metabolism as follows –
- Cortisol retards glucose consumpiton and protein synthesis, but promotes breakdown of proteins and fats in the cells of such parts of body as are concerned with normal (non-emergent) activities and defense. These parts include skin, alimentary tract, bones, lymph nodes, adipose tissue, muscles, Consequently, levels of glucose, FFAs and amino acids in blood pressure is elevated. This effect of cortisol in antagonistic to

SINUSOIDS

TRIBUTARY OF CENTRAL VEIN

ZONA RETICULARIS

MEDULLA (EPINEPHRINE, NOREPINEPHRINE)

that of insulin.

Effects of glucocorticoids upon liver are These promote

Fig. – Adrenal gland with a part cut to show cortex and medulla

intake of glucose, FFAs and amino acids by cells of liver. Then, these intensify deamination of amino acids, synthesis of urea, synthesis of glucose from fatty acids and amino acids (gluconeogenesis), and synthesis of glycogen from glucose (glycogenesis) in liver cells.

Cortisol is anti-inflammatory. It retards the migratory movements and phagocytic activities of white blood corpuscles (WBCs), suppressing “inflammation reactions” which constitute the normal defense mechanism of body against toxic substances. Simultaneously, it reduces the number of mast cells, reducing secretion of histamine. This is also an anti-inflammatory It also demotes synthesis of collage fibres which usually form at the sites of

inflammation in normal defense. That is why, cortisol is usually injected as a drug for treatment of diseases that are caused by deposition of collagen fibres, such as arthritis or rheumatism.

Cortisol is also “immunosuppressive“. It suppressess synthesis of antibodies, retarding the normal immune reactions of body against antigens and attack of micro-organisms. In fact, it induces atrophy of thymus gland and other lymphoid tissues, so that the productions of lymphocytes is That is why, it is used for treatment of allergy. Also, it is used in transplantation surgery to suppress the formation of antibodies in the body of recipients so that the latter may accept the transplanted organs.
Cortisol increases RBC count, but decreases the WBC count of It also elevates blood pressure (BP).

Sex hormones : The zona reticularis of adrenal cortex secrets androgen and estrogen in small These hormones regulates the development of sex organs, secondary sexual characters and promote growth and protein metabolism.
Role of adrenal cortex in stress reaction : Adrenal glands provide the body with an emergent “chemical defence mechanism” in stress conditions that threaten the physical integrity and chemical constancy of the After the “Fight or Flight” reaction, the body remains in a state of shock for some time just like a country after a war. Heartbeat, cardiac output, blood pressure and glucose and salt concentrations in ECF considerably go down in this “shock condition”. For example, excessive bleeding in an accidental injury immediately sends the body into shock condition. the injured must be made to recline and his / her legs must be elevated by putting a few pillows under the feet and hips. This increases venous flow of blood towards the heart, so that the cardiac output is maintained.

Whereas the hormones of adrenal medulla elevate O_2– consumption, BMR, respiration and tension to increase alertness and responsivity to prepare the body for violent stress-reactions, those of adrenal cortex, particularly aldosterone and cortisol, serve to maintain the body in living condition and recoup it from the severe after-effects of stress reactions. An increased output of cortisol is actually “life-saving” in shock conditions. It inhibits the normal defence mechanisms and mobilises help from all parts of the body in order to keep the body alive. In case the stress reaction is very strong and the shock is very severe, the life-saving mechanism fails, and the body succumbs to the resultant large scale muscle wasting and severe exhaustion. That is how a person sometimes dies mainly due to stress and shock, even when bitten by a non-poisonous snake. In a person succumbing to death, breathing becomes noisy, fretful and intermittent at short and then gradually longer intervals.

Adrenal glands are large in fetus, but these mainly secrete sex hormones. By the time of child-birth, these become small and their secretions remain minimal for a few days after birth. Obviously, the “chemical defence system” is very weak in newly born infants. The latter can, therefore, easily succumb to stress conditions. That is why, infants are provided extra care in maternity homes.

As is clear from above account, adrenal cortex is very necessary for survival, but adrenal medulla is not so necessary, because its deficiency can be compensated by sympathetic nervous system.

Control of adrenal cortex secretions : Secretion of glucocorticoids and sex hormones by adrenal cortex is regulated by a hormone, corticotropin or adrenocorticotropic hormone (ACTH), secreted by the anterior lobe of pituitary Secretion of ACTH from pituitary is, in turn, regulated by a “corticotropin-release hormone (ACTHRH)” of hypothalamus. A “feedback control mechanism” operates between hypothalamus, pituitary and adrenal cortex. A decrease in cortisol level in blood stimulates the hypothalamus and pituitary. Hence secretion of ACTHRH from hypothalamus and of ACTH from pituitary and, therefore, of glucocorticoids and sex hormones from adrenal cortex increases. When cortisol level in the blood rises, the control mechanism operates in reverse direction. This “feedback control” is very efficient and quick. It even observes a daily (circadian) rhythm because amount of ACTH and cortisol in blood is maximum during morning hours and minimum at midnight.

Secretion of mineralcorticoids is only nominally under the control of ACTH. Although adrenal glands themselves regulate secretion of mineralocorticoids according to Na⁺, water and K⁺ levels in ECF, by feedback, but this regulation is mainly provided by the kidneys. As the blood pressure goes down due to decreased amount of salt and water in blood, certain cells of afferent arterioles that supply glomeruli secrete an enzyme named renin. Reaching in blood, renin covers a plasma protein, angiotensinogen into angiotensin I. the latter is taken from blood by liver cells which release it back into the blood after converting it into angiotensin II. The latter is a hormone which stimulates adrenal cortex to secrete more aldosterone.

Hormones of adrenal medulla : The chromaffin cells of adrenal medulla synthesize two hormones adrenalin or epinephrine (80%) and nor-adrenalin or non-epinephrine (20%). These hormones are proteinous in nature and derived from amino acid tyrosine. Which is first hydroxylated and decarboxylated to form dopamine and than the latter is hydroxylated again to finally form Epinephrine is derived by methylation of norepinephrine.

Tyrosine ¾¾Hyd¾roxy¾lati¾on ® Dopamine ¾¾Hyd¾roxy¾lati¾on ® Nor epinephrine ¾¾Meth¾ylat¾io¾n ® Epinephrine

Decarboxylation

The molecular structure of dopamine, norepinephrine and epinephrine, includes a 6-carbon ring connected to two hydroxyl groups (– OH). This is called catechol ring, and these compounds are called catecholamines for this reason. Epinephrine (adrenalin) was first extracted by Abel (1899) who coined this name for it. It was, however, extracted in pure form by Jokichi and Takamine (1900). Its molecular structure was worked out by Aldrich in 1901. Stolz (1904) and Dakin (1905) synthesized it in their laboratories. Norepinephrine was discovered by Ulf von Euler (1946). Effects of these hormones were studied by Axelrod (1965). For their discoveries. Euler and Axelrod won

Nobel Prize in 1970.

Chromaffin cells store adrenaline and noradrenaline in secretory granules and release these by exocytosis when required. In blood, both hormones circulate in original active form. these retard the activity level of some of their target cells, but increase the activity level of most of their target cells. In their action mechanism, these affect the metabolic processes either by modifying the ion permeability of the plasma membrane of target cells, or by inducing formation cAMP.

(a) Function of epinephrine

Epinephrine causes constriction of the blood vessels (vasoconstriction) which supply blood to those peripheral and abdominal organs (skin and organs of digestive, excretory and reproductive systems) that normally remain active while we are resting or sleeping. Obviously, the activities of these organs are retarded, but the blood pressure (BP) increases.
Reduced supply of blood causes a pale skin (pallor), but arrector pilli muscles of skin contract, causing
Mouth becomes dry due to poor secretion of saliva.
Food digestion is retarded because of reduced gut peristalsis due to relaxation of the smooth muscles of gut wall, as well as, because of poor secretion of digestive
Kidneys produce small volume of urine, and muscles or urinary bladder
In pregnant women, the muscles of uterus contract, increasing the possibility of
Epinephrine causes dilation of blood vessels (vasodilation) which supply brain, skeletal muscles, heart, lungs, liver, adipose tissues, sensory organs, etc. Due to increased blood supply, these organs become very active, inducing alarm Obviously, the blood pressure, increased due to effect of norepinephrine, is reduced to some extent.
Pupils dilate due to contraction of radial dilatory muscles of Secretion of tear by lacrimal glands increases.
Epinephrine causes relaxation of the smooth muscles of trachea, bronchi and bronchioles. These organs, therefore dilate, so that breathing becomes easier and Remember that epinephrine is used in treatment of asthma for this reason.

Contractions of cardiac muscles intensify, increasing both rate and force of heartbeat, pulse rate, arterial pressure and cardiac
Due to an increase in adhesiveness of blood platelets, the time of blood clotting is considerably reduced.
The spleen contracts, releasing its reserve of blood corpuscles whose number in blood, therefore,
In islets of Langerhans in pancreas, secretion of insulin hormone decreases, but that of glucagon increases. Glucagon causes glycogenolysis, e. breakdown of glycogen into glucose in liver and skeletal muscles. Consequently, skeletal muscles become more active and liver cells release more glucose into the blood. Simultaneously, desgradation of fat (lipolysis) also occurs in adipose tissues, so that free fatty acids (FFA) increase in blood.
Because of an increase in blood levels of O₂ glucose, FFA, etc the basal metabolic rate of all body cells considerably increases and renders the whole body highly active and
External genitalia become flaccid, but ejaculation becomes early and

Since the rate and force of the activities of most internal organs increase in a few seconds under the effects of epinephrine and norepinephrine, the various changes can be detected by a lie detector polygraph to ascertain the emotional state of a person.

Difference between Adrenal cortex and Adrenal medulla

S.No.	Adrenal cortex				Adrenal medulla
1.	It is external firm region of the adrenal gland.				It is central soft region of the adrenal gland.
2.	It is pale yellowish-pink in colour.				It is dark reddish-brown in colour.
3.	It is enclosed by a fibrous capsule.				It is not enclosed by a fibrous capsule.
4.	It forms about 80% of the adrenal capsule.				It forms just 20% of the adrenal gland.
5.	It develops from the mesoderm.				It develops from the ectoderm (neural crests).
6.	It consists of 3 concentric regions : Outer zona glomerulosa, middle zona fasiculata and inner zona reticulars.				It is not differentiated into regions.
7.	It is essential for life, its destruction causes death.				It is not essential for life, its destruction does not cause death.
8.	It secretes 3 groups of hormones : mineralocorticoids, glucocorticoides and sexocortocoids.				It secretes 2 similar hormones nor adrenaline and adrenaline.
9.	It is stimulated to adrenocorticortrophic pituitray.	release its hormone	hormones from the	by the anterior	It is stimulated to secrete its hormones by nerve impulses reaching via sympathetic nerve fibres.
10.	There is no cooperation between adrenal cortex and sympathetic nervous system.				Adrenal medulla and sympathetic function as an integrated sympatheticoadrenal system.	nervous system	system called
11.	It causes many deficiency / excess disorders.				It is not known to cause any disorder.

Significance of adrenal medullary hormones

Relationship between adrenal medulla and sympathetic nervous system : Our routine in voluntary activities like food digestion, respiration, heartbeat and blood circulation, thermoregulation, peristalsis of tubular organs, secretion of glands, excretion, etc are continuously and automatically done by our internal (visceral) organs without the conscious control of our brain. These are, therefore, called involuntary activities, these activities occur under the control of autonomic nervous system and their co-ordinated regulation is controlled by the hypothalamus of brain. The autonomic nervous system controls these activities by affecting the activity levels of cardiac muscles, smooth muscles of visceral organs and blood vessels, and the glands. The autonomic nervous system comprises two

control systems, having antagonistic effects of these organs. These are sympathetic and parasympathetic systems. Obviously, the motor nerve fibres of both these systems, originating from central nervous system (CNS), innervate most of the internal organs. The motor fibres of parasympathetic system stimulate those organs which remain more active while we are at rest or sleeping. contrarily, the motor fibres of sympathetic system stimulate those organs which remain more active when we are awake and doing work.

The fibres of sympathetic system, innervating the organs, the postganglionic motor fibres. At their terminals, these release norepinephrine, a neurotransmitter which triggers an alteration in the activities of concerned organs. The adrenal medulla is also innervated by fibres of sympathetic system, but these are preganglionic fibres of this system. At their terminals these fibres release acetylcholine which stimulates chromaffin cells to release their hormones – epinephrine and norepinephrine. Circulating in blood, these hormones reach into the internal organs and not only increase the effects of sympathetic stimulation, but also prolong these effects about ten-fold. That is why, the sympathetic system and adrenal medulla are collectively considered as sympathoadrenal system, and the hormones of adrenal medulla are called sympathomimetic amines. Besides this, the medullary hormones, especially epinephrine, increase the basal metabolic rate (BMR) of all body cells, increasing the activity and irritability level of whole body. Since, however, the effects of sympathetic system and adrenal medullary hormones are complementary, a retarded efficiency of any one of these is compensated by the other.

Modern scientists have discovered that cells resembling chromaffin cells occur in small groups near the thoracic and abdominal ganglia of sympathetic system. These groups have been named paraganglia.

Alarm or stress reaction : Physico-chemical changes continuously occur in the external and internal environments of our body during our daily routine life, and our body keeps on maintaining homeostasis and functional equilibrium by counteracting the effects of these changes by alterations and co-ordinated regulations of the activities of various organs by sympathetic system under hypothalamic control. However, the emergency or stress conditions such as fear, anger, intense pain, accident and injury, burning, intense cooling or heating of body, sudden invasion of micro-organisms, poisoning, emotional upsets due to insult, restlessness, mental tension, anxiety, exertion, surgery, etc tend to disturb homeostasis and functional equilibrium to such an extent that the very survival of body in endangered.

As the sensory impulses of such strong stimuli called stressors, reach the brain, directly or through spinal cord, motor impulses or required responses are issued by hypothalamus to all organs, including adrenal medulla through the spinal cord. Consequently, norepinephrine is released simultaneously in all organs by sympathetic fibres, and a large amount of both epinephrine and norepinephrine is poured into blood by adrenal medulla. This “mass release” of these hormones prepares the whole body, within seconds, for a violent physical reaction called alarm or stress reaction, and often referred to as general adaptation syndrome (GAS). In this reaction, the concerned person either boldly faces the emergency, or tries somehow to escape from it. That is why, it is called “Fight or Flight reaction”.

(iv) Effects of irregularities of adrenal secretion

Hyposecretion : This may be a genetic defect. Undersecretion of adrenocorticoids (hypocorticism) causes Addison’s disease which is relatively rare and occurs in both men and women between the ages of 20 to 40 This disease was first discribed by Thomas Addison in 1849, 1855. It is maintained in following symptoms –
- Owing to low aldosterone level in blood, considerable amount of sodium ions and water is excreted in urine, leading to dehydration, low blood pressure, and weakness, all symptoms of a peculiar, Addinosonean anaemia which is different from common pernicious anaemia resulting from entirely different causes like diarrhoea, cholera,

Owing to low cortisol level, glucose level also falls in blood (hypoglycemia). This sharply reduces BMR in body Due to hypoglycemia and hyperkalemia (increased K⁺ level in blood) efficiency of brain, liver, skeletal and cardiac muscles, etc declines. Body temperature also falls. Heartbeat may even stop, causing death.
Decreased cortisol level induces gastro-intestinal disorders, resulting in loss of appetite, nausea, vomiting, diarrhoea, abdominal pain and
Due to a sharp decline in body’s chemical defense and resistance, sensitivity to cold, heat, infection, poisoning and other adverse condition Acute hypocorticism is catastrophic and resistance, sensitivity to cold, heat, infection, poisoning and other adverse conditions increases. Acute hypocorticism is catastrophic and threatens life. Complete destruction of removal of adrenals causes death in a short time, principally because of loss of excessive sodium in urine.
Addison’s disease also causes an increase in the number of WBCs, resulting into eosinophilia, lymphocytosis, leucocytosis,
Undersecretion of sex hormones causes impotence in males and disorders or menstrual cycle in
Excessive deposists of melanin, particularly in the skin of open parts of body like face, hands, feet, neck, teats, etc cause deep bronzing of skin in these
As increase in H⁺ concentration in blood may cause

Hypersecretion : Oversecretion of adrenocorticoids (hypercorticism) causes following disorders and diseases –
- Glucose level rises in blood (hyperglycemia). This may lead to diabetes mellitus.
- Irregular deposits of fat, particularly in thoracic parts and face, imparts asymmetrical shape to the the face becomes red and rounded (moon face), shoulders swell (buffalo humps) and abdomen dilates and often shows lines of stretching. All these are symptoms of Cushing’s disease (Cushing, 1932). Patients may die from brain haemorrhage, cardiac arrest, pneumonia, etc.
- Retention of sodium and water is the ECF increases blood pressure, causing severe hypertension and associated symptoms like severe headache. Fluids may accumulate at placed in connective tissue, causing edema, liver cirrhosis,
- Excessive loss of potassium in urine causes potassium deficiency (hypokalemia). This leads to muscular weakness and convulsions and nervous disorders, and may even cause tetany and paralysis, copious and frequent urination (polyuria) and thirst, bed urination (nicturia), Similarly, excessive loss of H⁺ in urine may cause alkalosis.
- Excessive mobilization of materials from all parts of body had widespread deteriorating effects. For instance, mobilization of proteins from all cells causes tissue similarly, mobilization from bones renders the bones weak and fragile

(osteoporosis).

Excessive secretion of male hormones (androgens) in a female fetus before

Fig. – A girl showing pseudohermaphroditism

complete formation of ovaries results into pseudohermaphroditism due to masculinization of external genitals, and causes abnormal development of muscles, hair on face (beard and moustache), early sexual maturation, hoarse voice and absence of menstruation. The clitoris grows to penis size, while vagina and uterus remain underdeveloped. This is known as adrenogenital syndrome. The resultant females are sterile. Oversecretion of

androgens after complete formation of ovaries and fallopian tubes causes only a moderate enlargement of clitoris. Oversecretion of androgens in girls after birth causes a gradual masculinization manifested in overgrowth of clitoris, under development of mammary glands and uterus and disturbed menstruation. Oversecretion of androgens in male children causes excessive development of penis (marcogenitosomia) and other secondary sexual organs and characteristics, but atrophy of testes so that there is no spermatogenesis. Early erections are noted. Due to the anabolic effects of androgens, both in girls and body, growth is accelerated, muscles are well-developed and strong, and bones mature early.

Excessive secretion of female hormones in adult males cause enlarged mammary glands (gynaecomastia) and retards growth of Contrarily, excessive secretion of androgens in females in masculinizing and causes hirsutism (increased facial and body hair and muscle growth, clitorial enlargement, etc.)

Prolonged undersecretion of catecholamines by adrenal medulla causes low blood pressure and depression. Regular treatment with antidepressant drugs, like cocaine, amphitamines, ephedrine, tyramine, etc., which stimulate the sympathetic nervous system, is required. Contrarily, the oversecretion of catecholamines causes high blood pressure and hypertension. Antihypertensives (transquilizers), like disulphiram, reserpine, guanethidine, etc are useful, because these retard the effects of sympathetic nervous system.

Pancreas

Location, origin : Pancreas (Gr. pankreas = sweet bread; Fr., pan = all + kreas = flesh) is a flattened and pinkish mixed gland situated in the concavity formed by duodenum just behind the stomach. It measures about 15 cm in length and 4 to 5 cm in It forms by fusion of two bilateral endodermal processes of embyronic intestine (duodenum of future adult).
Structure : About 98% part of the gland is exocrine and

formed of hollow pancreatic acini or lobules embedded in a

ALPHA (a) CELLS BETA (b) CELLS

connective tissue stroma. In the stroma, there are numerous (approximately 1 to 2 million in human pancreas) small (0.1 to 0.2 mm in diameter) clusters of endocrine cells, called islets of Langerhans after the name of their discoverer, Paul Langerhans (1869).

Each islet of Langerhans contains hundreds of small cells and several blood capillaries and sinusoids. Its cell are distinguished into four types –

Beta (b) cells (about 70%) in the middle of the islet.
Alpha (a) cells (about 20%) in cortical zone of the islet.
Scattered delta (d) or gamma cells (about 5%)

LSIET OF LANGERHANS

BLOOD VESSEL

(GLUCOGON)

PANCREATIC ACINI

(INSULIN)

d CELLS (SOMATOSTATIN)

The remaining F or PP cells (about 5%).

Fig. – T.S. of pancreas

Hormones of pancreas and their role : The b and a cells of islets of Langerhans respectively secrete insulin and glucagon hormones which are important regulation of carbohydrate protein and fat metabolism in the

Insulin : In 1889, Minkowski and Mehring discovered that pancreas is related with the disease of diabetes mellitus in Normal concentration of glucose in blood is about 100 mg (0.1 gm) per 100 ml. It increases somewhat after a carbohydrate rice food. Then, the secretion if insulin increases. It increases the permeability of all

cells for glucose several times, except that of brain cells and red blood corpuscles (RBCs). The brain cells and RBCs are already highly permeable to glucose. After taking more glucose from blood, the cells utilize it for energy- production. Consequently, the basal metabolic rate (BMR) and RNA and protein synthesis increases in cells. Simultneously, glycogenesis (synthesis of glycogen from glucose) in liver and muscles and lipogenesis (synthesis of fat) in adipose tissues also increase. Thus, acting as an anabolic hormone, insulin contributes to proper growth and repair of body and maintenance of food reserve in between the meals.

In 1923, two Canadian scientists, Banting and Best succeeded in preparing a pure extract of insulin from the pancreatic islets of a new born calf with the help of Macleod, Banting and Macleod won the 1923 Nobel prize for this work. Later, Abel (1926) succeeded in preparing pure crystals of insulin. F. Sanger (1955) worked out the molecular structure of bovine insulin and won the 1958 Nobel Prize. He discovered that insulin is a small protein whose molecule consists of two polypeptide chains, a and b, joined by disulphide linkages and respectively formed of 21 and 30 amino acid residues. Insulin is the first protein to be crystallized in pure form, first protein whose molecular structure was worked out, the first protein to be synthesized in laboratory in 1964, and also the first protein to be commercially manufactured by means of DNA recombinant technique. Even the human insulin was also synthesized by Tsan in 1965.

Hypoinsulinism : In insulin deficiency, body cells fail to obtain glucose from Hence, glucose level of blood rises, a condition called hyperglycemia. When glucose level rises further, glucose starts passing out in urine. This condition is called glycosuria. Ultimately, when glucose level in blood rises to 300 to 500 mg per ml, the person concerned suffers from diabetes mellitus in which the urine becomes sweat.

Diabetes mellitus has been known to Greeks as a human disease since 1500 B.C. in England, it was known as a “pissing evil” due to copious urination in it. Modern scientists have discovered that diabetes mellitus is of two types

– I and II. The type I diabetes is usually found in young people, in some of which it is hereditary. About 10% of diabetes patients suffer from this type. Other patients suffer from diabetes of type II, usually found in people of over 40 years of age or obesse persons. Diabetics excrete large volumes of urine. This is called polyuria. It results into dehydration which, in turn, causes increased thrist (polydipsa) and hunger (polyphagia). Being unable to utilize glucose for energy-production (“starving in midst of plenty”), the cells utilize their proteins for it, causing “body wasting”. The body, therefore, becomes very weak. Nervous system may be damaged and often cataract occurs. Lipolysis in adipose tissues increases, elevating blood level of free fatty acids (FFA). Accelerated, but incomplete, oxidation of fatty acids for energy, especially in liver, results into the formation of ketone bodies – acetone, acetoacetic acid and b-hydroxybutyrate– , causing ketosis. Since the ketone bodies are sweet, acidic and poisonous, their increased amount in blood causes acidosis. Hence, patients may anytime become unconscious (coma condition) and finally die.

Regular injections of insulin must be given to chronic patients of diabetes. Balanced diet, exercise, and regular intake of insulin tablets (eg dionyl) may keep diabetes in control. Certain drugs, like glyburide, which stimulate insulin secretion are now available.

Hyperinsulinism : Oversecretion of insulin enhances glucose intake by most body cells and glycogenesis in liver and muscles, causing a persistent decrease in blood glucose level (Hypoglycemia) since brain cells and cells of retina and germinal epithelium mainly depend on glucose for energy, nervous efficiency, fertility and vision sharply Poor supply of glucose to the brain stimulates sympathetic nervous system, causing unnecessary excitement and feeling of anxiety, sweating, weakness, fatigue and muscular convulsions. Continued excess of

insulin in blood causes “coma (insulin shock)” and death. Injections of cortisol, adrenaline, growth hormone and glucagon help in treatment of hyperinulinism, because these hormones retard glucose utilization in cells and mobilize glucose and fatty acids respectively from liver and adipose tissues. Injections of glucose also give relief to the patients.

Glucagon : This is secreted by the alpha cells of islets of It was discovered by Kimball and Murlin (1923). Like insulin, it is also a small protein. Its molecule consists of a single polypeptide chain of 29 amino acid residues. Its function is to elevate glucose level in blood when glucose is deficient. For this, glucagon intensifies glycogenolysis, deamination and gluconeogenesis, and inhibits glycogenesis in liver cells. It also intensifies lipolysis in adipose tissues. Thus, it is promoter of catabolic metabolism. When, during excessive physical labour and stress, glucose consumption in the body increases and blood glucose level falls, glucagon is secreted to normalize the glucose level.

The secretion of insulin and glucagon is regulated by a “limit-control feedback” or “push and pull feedback” control system. When sugar level in blood increases, insulin is secreted and secretion of glucagon is inhibited. When, due to the effect of insulin, blood sugar level falls, secretion of insulin is inhibited and that of glucagon is stimulated. Besides this, certain amino acids (e.g. orginine and leucine), gastro-intestinal hormones, acetylcholine, etc enhance insulin secretion. Contrarily, diazoxide, phenytoin, alloxan, etc inhibit insulin secretion by destroying the b cells of islets of Langerhans.

Somatostatin and Pancreatic polypeptide : Modern physiologists have postulated that the d and F (PP) cells of pancreas respectively secrete somatostatin (SS) and pancreatic polypeptide (PP). Somatostatin resembles the growth hormone inhibitory hormone (GHIH) secreted by Its molecule is a small peptide of 14 amino acid residues. Acting as a paracrine hormone, it serves to retard secretory activities of a and b cells. Besides this, it also slows down food digestion, absorption of digested nutrients and assimilation of nutrients in cells. Thus, it prolongs utilization of every feed. pancreatic polypeptide (PP) also acts as a local, paracrine hormone. It retards secretion of pancreatic enzymes and somatostatin. It also inhibits motility of stomach, duodenum and gall bladder.

Difference between diabetes mellitus and diabetes insipedus

S.No.	Diabetes mellitus	Diabetes insipidus
1.	It is due to deficiency of insulin.	It is due to deficiency of ADH.
2.	The blood sugar becomes high and glucose appears in urine.	The blood glucose is normal and glucose does not appear in urine.
3.	There is high blood cholesterol and ketone body formation.	There is no such phenomenon.

Important tips

Thymus gland

Origin and position : The thymus gland is located in the upper part of the thorax near the It is endodermal in origin, arising in the embryo from the epithelium of outer part of third branchial pauches.

Structure : Structurally, it is like lymph gland enveloped by a thin, loose and fibrous connective tissue capsule. Septa, extending inwards from the capsule, divide the two lobes of the gland into a number of small Each lobule is distinguished into a cortical parenchyma containing numerous lymphocytes, and a medullary mass of large, irregularly branched and interconnected epithelial cells (reticular cells), a few lymphocytes and some phagocytic cells called macrophages or Hassal’s

corpuscles.

RIGHT SUBCLAVIAN VEIN

RIGHT LUNG

DIAPHRAGM

THYROID GLAND

LEFT SUBCLAVIAN VEIN

THYMUS GLAND

LEFT LUNG HEART

(iii) Function of thymus glands

Fig. – Location of thymus gland

Thymus is haemopoietic, as well as, an endocrine gland. Thymus is the “seedbed” of “thymic lymphocytes (T-lymphocytes). Certain “stem cells”, originating in yolk sac and liver in early embryo, but only in bone marrow in late embryo, migrate into the thymus and proliferate to form a large number of
The major function of thymus is to secrete thymosin hormone, thymic humoral factor (THF), thymic factor (TF), These compounds induce, not only the proliferation of lymphocytes, but also their differentiation into a variety of clones differently specialized to destroy different specific categories of antigens and pathogens likely to get into the body. This is called maturation of lymphocytes. Thus, the thymus brings forth competent T-lymphocytes for cellular immune defense system of body, and maintains a sufficient supply of these lymphocytes in general blood circulation and peripheral lymphoid organs and tissues for future use.
As is clear from above account, thymus is essential in neonatal (newly born) infant and postnatal child for normal development of lymphoid organs and cellular immunity. That is why, the thymus, small at birth, progressively grows in size about three or four-folds upto about the age of By this time lymphoid organs and tissues are well-developed. The thymus, therefore, starts gradually diminishing in size and its tissue is progressively infiltrated by yellowish adipose tissue. This is known as the “immunity theory of ageing”. By the old age, the thymus is reduced to quite a thin, yet functional chord of tissue.

Pineal gland (Epiphysis)

Origin, position and structure : This is a small, whitish and somewhat flattened ectodermal gland situated at the tip of a small, fibrous stalk that arises from dorsal wall of diencephalon, e. the roof (epithalamus) of third ventricle of the brain. Due to its location, it is also called epiphysis cerebri. It is covered over by a thin capsule formed of the piamater of the brain. Septa from this membrane extend into the gland, dividing in into lobules having two types of branched cells, viz the large and modified nerve cells, called pinealocytes, and interstitial or neuroglial cells forming the supporting tissue. In the pineal gland starts degenerating after the age of about 7 years because of deposition of granules of calcium salts (brain sand) in it.

Function of pineal body : Hormone, though the function of the gland is still the subject of current research, it is known to secrete one hormone, Melatonin concentration in the blood appears to flow a diurnal (day-night) cycle as it arises in the evening and through the night and drops to a low around noon. Melatonin lightens skin colour in certain animals and regulates working of gonads (testes and ovaries). Light falling on the retina of the eye decreases melatonin production, darkness stimulates melatonin synthesis. Girls blind from birth attain puberty earlier than normal, apparently because there is no inhibitory effect of melatonin on ovarian function.

Serotonin, a neurotransmitter found in other locations in the brain, is also found in the pineal gland. Research evidence is accumulating to support the idea that the pineal gland may be involved in regulating cyclic phenomena in the body.

Gonads

The gonads are the sex glands, the testes and the ovary. Testes is the male gonad and ovary is the female gonads. They develop from the mesoderm of the embryo. They produce gametes (sperm and ova). Besides producing gametes, the gonads secrete sex hormones from the onset of puberty (sexual maturity) to control the reproductive organs and sexual behaviour.

The sex hormone were discovered by Adolf Butenononal in 1929 and 1931. He won the 1939 Nobel prize jointly with Leopold Ruzicka.

(i) Testes

Location and structure : In testes between the siminiferous tubules, special types of cells are present called interstitial cells or cells of leydig. These cells secrete male hormones (androgens) derived from The main androgen is testosterone other less important androgens include

VAS DEFERENS

EPIDIDYMIS

INTERSTITIAL CELLS (CELLS OF LEYDIG)

SPERMATO- ZOANS

androstenedione and dehydroepiandrosterone. It is a masculinizing hormone. From puberty to the age of about twenty year i.e. adolescence or the period of sexual

RETE TESTIS

SEMINIFEROUS TUBULE

SERTOLI CELL

GERMINAL EPITHELIUM

CONNECTIVE TISSUE STROMA

BLOOD VESSEL

maturation or attainment of adult hood.

(b) Function

Fig. – Ultrastructure of testes

It stimulates the male reproductive system to grow to full size and become
It stimulates the formation of sperms (spermatogenesis) in the seminiferous
It stimulates the development of male accessory sex characters such as hair on the face (beard and moustaches), growth and distribution of hair on the body, deepening of voice, broadening of shoulders, enlarged and stronger bones and It also maintains these characters.
It also determines the male sexual behaviour sex urge, aggressive
Under its effect protein anabolism

Grythropoisis in bone marrow
In brief, testosterone determines It is also required, together with the follicle stimulating hormone (FSH) of pituitary, for initiation and completion of spermatogenesis. All androgens are also secreted in traces from adrenal glands in both boys and girls.
Development of testis : Under the effect of chorionic gonadotropic hormone, secreted by placenta during pregnancy, the testes of eight to nine months old fetus start secreting testosterone. The latter regulates differentiation and development of urinogenital system, accessory genital organs and external genitalia in the During childhood i.e. from birth to puberty (age of 11 to 13 years), testes remain quiescent, so that androgens are not secreted. At puberty, the gonadotropic hormones (FSH and ICSH) of pituitary reactivate the testes which, therefore, start producing sperms and resume secreting androgens. Upto the age of about 40 years, androgens are secreted in sufficient amounts. thereafter, their secretion starts gradually declining, but the capability of reproduction still continues for many years.
Castration : Surgical removal of testes is called castration or orchidectomy. Castration, or deficient secretion of testosterone (hypogonadism) before puberty (due to congenital defects or injury to testes) retards growth of genitalia, muscles and bones, as well as, the development of sexual Consequently, the affected person develops into a sterile neuter or eunuch (eunuchoidism). Eunuchs are relatively taller with longer limbs, but lean and weak in constitution. Their genitals are of child-size. Beard and moustache do not usually grow. Aggressiveness is reduced. In brief, the libido is diminished in eunuchs.

Castration or hypogonadism after puberty preserves the libido, but diminishes its overall efficiency (demasculinization). Muscular strength, hair growth, spermatogenesis, sex urge and potency sharply decline. sometimes, the person becomes impotent.

Castration is widely used in animal husbandry and domestication. Castrated cattle, horses and fowls are respectively called steers, geldings and capons. Castration makes these docile.

Ovary : Primordial ovarian follicles are formed in the primitive ovaries of female fetuses as early as about 16 weeks of gestation, but these do not secrete Even in early childhood, upto the age of 7 or 8 years, ovaries remain quiescent. Thereafter, the pituitary starts secreting gonadotropins (FSH and LH) under whose influence puberty in girls sets in at about the age of 11 to 13 years; ovaries become active and menstrual cycle begins, so that the girls attain sexual maturity. Reproductive period, i.e. ovarian function and menstrual cycles in women normally cease at about the age of 45 to 55 years. This is called menopause. It usually results in a rise in urinary excretion of gonadotropins of the pituitary gland.
Ovarian hormone : Under the influence of FSH and LH. They secretes three female sex hormone, estrogen, progesteron and They derived from cholesterol.
- Estrogens : These are secreted by the cells of the Graafian (ovarian) follicle surrounding the maturing ovum in the They stimulate the female reproductive tract to grow to full size and become functional. They also stimulate the differentiation of ova (oogenesis) in the ovary. They also stimulate the development of accessory sex characters such as enlargement of breasts; broadening of pelvis; growth of pubic and axillary hair; deposition of fat in the thighs, and onset of menstruation cycle. Graafian follicle cells are stimulated to secrete estrogens by luteinising hormone (LH) from the anterior lobe of the pituitary gland. Rise of blood-estrogens level above normal inhibits the secretion of LH from the anterior pituitary. This negative feedback prevents the oversecretion of estrogens.

Progesterone : It is secreted by the corpus luteum. The latter is a yellowish body formed in the empty Graafian follicle after the release of the

ovum. Its hormone suspends ovulation during pregnancy, fixes the foetus to the uterine wall, forms placenta, and controls the development of the foetus in the uterus. Ovulation, formation of corpus luteum and secretion of progesterone are stimulated by the luteinsing hormone (LH) from the anterior pituitary.

PRIMORDIAL FOLLICLE

BLOOD VESSELS IN HILUS OF OVARY

CORPUS ALBICANS

SECONDARY (ANTRAL)

FOLLICLE

PRIMARY (PREANTRAL)

FOLLICLE

GERMINAL EPITHELIUM TUNICA ALBUGINEA

CORTEX OF STROMA

FOLLICULAR FLUID IN ANTRUM

MATURE (GRAAFIAN) FOLLICLE

CORPUS HEMORRHAGICUM (RUPTURED FOLLICLE)

Relaxin : It is produced by the corpus luteum at the end of the gestation It relaxes the cervix of the uterus

MATURE CORPUS LUTEUM

BLOOD CLOT

EARLY CORPUS LUTEUM

MEDULLA OF STROMA

CORONA

RADIATA

OVULATION DISCHARGES A SECONDARY

and ligaments of the pelvic girdle for easy birth of the young one.

Fig. – V.L.S. of ovary

OOCYTE

Regulation of ovarian hormone : Secretion of estrogens is regulated by the gonadotropins of pituitary. Undersecretion of estrogens (hypogonadism) before puberty due to congenital defects or damage to ovaries, causes female eunuchoidism. Accessory genitals and breasts remain underdeveloped, pelvis remains narrow and buttocks Secondary sexual characteristics also do not develop. Hypogonadism in adulthood reduces fertility and disturbs menstrual cycles. Oversecretion (hypersecretion of hypergonadism) of estrogens also disturbs menstrual cycles and may even cause cancer.

Hormonal sexual abnormalities

True hermaphroditism : All higher animals and some higher plants are unisexual (dioecious) organisms with separate male and female individuals. Occasionally, bisexual (hermaphrodite or monoecious) individuals, displaying characteristics of both male and female sexes, are seen in these organisms. This aberrant sexuality develops mainly due to genetic abnormalities, or hormonal disbalances. Bisexuals produced due to genetic abnormalities are regarded true hermaphrodites.

Pseudohermaphroditism : Bisexuals produced due to hormonal disbalances are regarded pseudohermaphrodites or intersexes. An intersex can be defined as an individual genetically belonging to one sex (i.e. having normal XY or XX sex chromosomes), but phenotypically displaying certain characteristics of the other sex. Obviously, intersexes possess normal glands (testes or ovaries), but their accessory reproductive organs (genital ducts and glands, etc.), external genitalia (copulatory organs) and secondary sexual characteristics (stature, voice, hair, breasts, body phsiology, etc.) and behaviour are ambiguous or at variance from their genetic (gonadal) sex. Obviously, these are sterile individuals (eunuchs).

Male intersexes develop when secretion of male hormones (androgens) is insufficient during embryonic development due to defective testes. Female intersexes, on the other hand, develop when the female fetus is exposed to a coipous supply of androgens mainly from adrenal glands.

Psychological sex abnormalities : In human beings, psychological disbalances produce homosexual, transvestite and trans-sexual individuals. These individuals are physically normal, yet they display unusual behaviour. For example, homosexuals prefer having sex with others of the same sex. Transvestites prefer to dress in

attirement of opposite sex in pursuit of sexual excitement. Trans-sexuals possess desire to belong to the opposite sex and many even prefer to undergo operations for this.

Freemartin : When male and female twin (fraternal twins) are produced in cattle, the male calf is normal, but the female calf is usually sterile, having masculanized reproductive organs. What happens in this case is that the twins share a common placenta, establishing a vascular connection between these. When male hormones of male calf circulate in female fetus, these supress sexual development in this fetus. Hence, the female calf circulate in female fetus, these supress sexual development in this fetus. Hence, the female calf prossesses rudimentary genital organ. Such calves are called freemartins.

Testosterone exerts a feed back inhibitor effect of pituitary LH(ICSH)
Estrogen supress the production of pituitary

Menarche is the starting of menstruation in girls at about 13 1

years.

Progesterone : Also called anti-abortion
Gravidex test : Involve testing of HCG of placenta in the urine to test the
Contraceptive pills : Contain oestrogens and progesterone so called combined These check ovulation and so pregnancy in female.
Adiposogenital syndrome : Also called hypothalmic eunuchoidism characterized by hypogonadism in male caused by genetic inability of hypothalamus to secrete gonadotrophin releasing

Hormonal Contraception

Female contraception : As already described, gonads are stimulated to produces sex cells (gametes) and secrete sex hormones by the gonadotropic hormones (FSH and LH) of anterior pituitary. The anterior pituitary is, in turn, stimulated to secrete gonadotropins by the gonadotropin-releasing hormone (GnRH) of hypothalamus. In women, FSH promotes oogenesis and secretion of female hormones (estrogens). LH promotes ovulation, formation of corpus luteum and secretion of progesterone from it. A negative feedback regulation operates between GnRH and gonadotropins, on one hand, and between gonadotropins and female hormones on the other. Hence, high concentration of female hormones retards secretion of FSH, LH and GnRH due to which oogenesis does not occur, and pregnancy is out of question. Thus, this negative feedback regulation is contraceptive. That is why, women who do not want pregnancy take oral contraceptive pills of estrogens or progesterone for first 21 days during menstruation cycle. Contraceptive pills of mixtures of estrogens and progesterone are more effective. The most popular contraceptive pills contain synthetic ethinyl estradiol and synthetic progesterone (e.g. norethindrone). In a modern method, a capsule of synthetic progesterone, like levonor gestrel, is implanted under the skin. The capsule serves for contraception for about five years.

Abortion is also now permissible in many countries to check population growth. Since progesterone is necessary to maintain early pregnancy, drugs, like mifepristone (RU-486), which inhibit the effects of progesterone are administered for abortion.

Male contraception : In men, LH stimulates cells of Leydig to secrete male hormones (androgens) of which testosterone is the principal hormone. Testosterone, in turn, inhibits LH secretion, but not FSH secretion by anterior

pituitary. FSH and testosterone stimulate spermatogenesis. It has been found that large doses of testosterone can inhibit secretion of gonadotropin-release hormone (GnRH) by thalamic cells, thereby inhibiting secretion of both LH and FSH by pituitary. Hence systematically administered injections of testerone have been suggestes as a means of male contraception.

Recently, the cells of Sertoli in seminiferous have been found to secrete a protein factor named inhibin which directly inhibits secretion of FSH by pituitary. Hence, use of inhibin as a male contraceptive is now being explored.

Gastro-intestinal mucosa placenta skin, kidney and heart

Gastro-intestinal mucosa : Inner most layer of the wall of the alimentary canal is called mucosa. Certain cell of the mucosa of the stomach and intestine secrete important hormones. Gastro-intestinal mucosa is endodermal in
Stomach : The mucosa of the pyloric stomach near the duodenum secretes a hormone called gastrin. Presence of food in the stomach provides a stimulus for gastrin secretion. Gastrin stinmulates the gastric glands to produce the gastric It also stimulates the stomach movements.
Intestine : The intestinal mucosa secretes six hormones : secretin, cholecystokinin, enterogastrone, enterocrinin, duopcrinin and villikinin. Entry of acidic food from the stomach into the duodenum serves as a stimulus for the release of these
- Secretin : It is produced by the small intestinal mucosa. It causes the release of sodium bicarbonate solution from the pancreas for pancreatic juice and from the liver for bile. It also inhibits the secretion and movements of
- Cholecystokinin-pancreozymin (CCK-PZ) : This hormone is secreted by the mucosa of entire small The actions of cholecystokinin and pancreozymin were discovered independently. But it has been discovered that both hormones have similar effects and hence it is considered one hormone. As the name suggest CCK-PZ has two main functions. The word cholecystokinin is derived from three roots : Chol meaning bile, Cyst meaning bladder, and kinin meaning to remove. The word pancreozymin is derived from pancreas and Zymin, which means enzyme producer. This hormone stimulates the gall bladder to release the bile and also stimulates the pancreas to release its enzymes.
- Enterogastrone : It is secreted by the duodenal mucosa. It shows gastric contractions and stops the secretion of gastric
- Enterocrinin : It is secreted by duodenal mucosa. It stimulates crypts of Lieberkuhn to secrete the enzymes in the intestinal
- Duocrinin : It is secreted by the duodenal mucosa. It stimulates the release of viscous mucus from Brunner’s glands into the intestinal
- Villikinin : It is secreted by the mucosa of the entire small It accelerates the movements of villi to quicken absorption of food.
Placenta : When the early embryo reaches into the uterus from fallopian tube, it becomes implanted with uterine wall by a placenta for support and The cells of placenta secrete two steroid hormones (estradiol and progesterone) and two protein hormones (human chorional gonadotropin-HCG and human placental stomato

mammotropin-HCS). Early placenta secretes so much of chorional gonadotropin that the latter starts being exerted in mother’s urine just after about two weeks of pregnancy. Its presence in urine is used for pregnancy test. It serves to maintain the corpus luteum, and to stimulate it for secretion. Due to its effect, the corpus luteum continues secreting estrogens, progesterone and relaxin. It also serves to maintain pregnancy by preventing contraction of uterine wall. After about three months of pregnancy, secretion of progesterone by the placenta increases. Hence, importance of corpus luteum decreases, and it starts degenerating. If therefore, ovaries are surgically removed at this stage, pregnancy remains unaffected, i.e. there is no abortion and the fetus grows and develops normally.

The placental somatomammotropin was formerly known as placental lactogen. Reaching into mother’s body, its serves as a mid growth hormone and promote growth of milk glands.

Relaxin hormone : This hormone has been obtained from corpus luteum ovaries and from the placenta. It is a polypeptide. During pregnancy it causes relaxation of the ligaments of pubic symphysis, and towards the termination of pregnancy, softens and widens the opening (cervix) of uterus for easy child birth (parturition). A temporary structure with endocrine function is placenta.

Skin : Vitamins of D group are synthesized in skin cells under the effect of ultraviolet (UV) rays of sunlight from cholesterol-derived Cholecalciferol (D₃) is the main D vitamin. It circulates in blood. Liver cells convert it into hydroxycholecalciferol (calcidiol) by hydroxylation and release back into blood. Certain cells of proximal convoluted tubules of nephrons in the kidneys convert calcidiol into dihydroxycalciferol (calcitriol) by further hydroxylation and release back into blood. Calcitriol is an important regulator of Ca²⁺ homeostasis. It promotes absorption of Ca²⁺ and phosphorus in intestine and bone-formation. It is therefore, required for growth of body and bone healing. Its deficiency in childhood causes thin, weak and curved bones, a condition called rickets. Its deficiency after growth period, causes weak, porous and fragile bones. This called osteomalacia.
Kidney : Whenever the rate of ultrafiltration in kidneys decreases due to low blood pressure (BP), the cells of juxtamedullary complexes secrete into blood a compound named renin. The latter is a proteolytic enzyme. It acts upon a large plasma-protein formed in liver and called angiotensinogen, separating a small protein from it called angiotensin-I. Besides their function of excretion, the kidneys secrete three hormones, viz calcitriol, renin and Calcitriol is the active form of vitamin D₃ as already described. While the blood flows in blood capillaries of liver, an angiotensin-converting enzyme (ACE) converts angiotensin-I into angiotensin-II which acts as a hormone. This hormone accelerates heartbeat and constricts arterioles increasing blood pressure. Consequently, the rate of ultrafiltration increases. Simultaneously, it stimulates adrenal cortex to secrete aldosterone, and enhances water and sodium reabsorption from nephrons. These factors also increase the volume of ECF, elevating blood pressure.

Erythropoetin (EPO) controls formation of enthrocytes (red blood corpuscles-RSCs) in red bone marrow. That is why, its secretion increases on decrease in blood volume, or RBC count, or haemoglobin deficiency (anaemia). Contrarily, its secretion decreases when RBC count tends to increase due to blood transfusion or other reasons.

Heart : When volume of ECF and blood pressure (BP) increase due to retention of more NaCl in the body, certain cardiac muscle cells of the atria of heart secrete an atrial natriuretic peptide (ANP) which acts as a The effect of ANP is to promote copious urination (diuresis) and excretion of NaCl (natriuresis) to normalise ECF volume and BP. It also inhibits the effect of vasoconstrictor hormones and secretion of renin, aldosteone and vasopressin hormones.

List of hormones their chemical nature and functions

Name of endocrine gland	Name of hormone and its chemical nature	Functions
(1) Neurosecretory cells of Hypothalamus (Supraoptic Nucleus and Paraventricular Nucleus)	(1) Oxytocin and vasopressin nanopeptide.	(i) Milk ejection and parturition (oxytocic effect). (ii) Vasoconstriction and antidiuretic (vasotocin) effects.
	(2) Gonadotropin releasing hormones	Stimulates FSH and LH sysnthesis.
	(3) Other releasing hormones e.g. TSHRH, MSHRH, ACTHRH, GHRH etc. Proteinaceous	Stimulate TSH, MSH, ACTH GH secretions from pituitary.
(2) Pituitary (a) Neurohypophysis (Pass Nervosa) (b) Adenohypehypsis (contains diverse cell types)
	Store and release Oxytocin and Vasopressin.	Hormone release is related to physiological state and requirements.
	Proteincaceous or glycoprotein	Affect growth, development differential pubertal changes and other metabolic mechanism.
(3) Pineal	Melatonin-derived from the amino acid tyrosine	(1) Antagonist to FSH / LH (2) Regulates biological / circadian rhythms.
(4) Thyroid gland (amine hormone) having – NH₂ group)	(a) Thyroxine, iodinated amino acid called tyrosine (T₂, T₃, T₄).	(a) Controls basal metabolic rate (BMR). All organ / system of body responds to thyroxine.
(4) Thyroid gland (amine hormone) having – NH₂ group)	(b) Thyrocalcitonin (Peptide)	(b) Facilitates Ca⁺² absorption
(5) Parathyroid gland	Parathormane, Peptide	Ca⁺² and PO^–₄ metabolism.
(6) Thymus	Thymosine (polypeptide)	Anti-FSH and LH; delays puberty
(7) Islets of lengerhans (= Endocrine pancrease) (i) a-cells (ii) b-cells (iii) d-cells	Glucagon Isolated by Insulin Banting Secretin Polypeptide	(i) Gluconeogenesis / Glycogenolys (ii) Glycogenesis (iii) Gastric functions
(8) Adrenal gland (a) Adrenal medulla (Amine hormone have – NH₂)
	(a) Catecholamines (epinephrine = adrenaline, and norepinephrine = noradrenaline (derived from tyrosine)	(a) Stresses = emergency = Fright, Fight and Flight Hormone (3F) acclerates cardiac functions muscle activity etc.
(b) Adrenal cortex	(b) Mineralcorticoids and glucocorticoids and traces of androgen and estrogen steroids derived from cholesterol	(b) Electrolyte and carbohydrate metabolism.
(9) Ovary (a) Ganulosa cells steroid, fat soluble have sterol group derived from cholesterol
	Estrogen (Steroid) Estrone, estradiol	(a) Secondary sex character primary action on uterine endometrium mitogenic.
(b) Corpus luteum	Estrogen and Progesterone (Steroid)	(a) Secreted during luetal phase of menstrual cycle in human female and oestrous cycle of other mammals. Prepares uterine endometrium for receiving blastocytes for implantation. Progesterone is also called pregnancy hormone and is anti-FSH and anti-

		LH/anti-LTH.
(c) Placenta temporary endocrine gland formed during pregnancy	(a) Steroid secreted are estrogen and progesterone (b) Relaxin-Polypeptide	(a) Maintenance of pregnant state, prevents lactogenesis folliculogenesis, and Ovulation. (b) Act on pubic symphysis and enlarges the birth canal to facilitate birth. Acts synergestically with oxytocin during this process (parturition)
(10) Testis (i) Sertoli cells (=sustentacular cells)	(i) Inhibin – Polypeptide	Inhibits FHS action and attenuates spermatogenesis decrementally
(ii) Leydig cells (=Interstitial cells)	(ii) Estradiol-Steroid Androgens (e.g. Testosterone) Steroid androstenedione)	–do– (i) Pubertal changes in male (ii) Secy. sex characters in male (iii) Sex drives (iv) Spermatogenesis
(11) Gastro-intestinal hormones (secreted by cells of mucosa of stomach and intestine) also called hormones		Stimulates gastric juices secretion from gastric gland, movement of sphincters of stomach and increased movement of stomach
(a) Pyloric stomach (Argentophil cells) Intestine	Gastrin (i) Secreten (ii) Cholecystokinin (CCK) (iii) Enterogastrone (iv) Duedocrinin (v) Enterokinin (vi) Villikrinin	(i) Stimulates secretion of succus entericus (ii) Bile released from gall bladder (iii) Inhibits gastric secretin (iv) Stimulates secretion of mucous from Brunner’s gland (v) Stimulate intestinal gland (vi) Stimulate villi movement

Disease caused by hormonal irregularities

Disease	Hormone	Quantity	Gland
Dwarfism	GH	Deficiency	Pituitary
Gigantism	GH	Excess	Pituitary
Acromegaly	GH	Excess	Pituitary
Simmond’s disease	GH	Deficiency	Pituitary
Diabetes incipedus	ADH	Deficiency	Pituitary
Cretinism	Thyroxine	Deficiency	Thyroid
Simple goitre	Thyroxine	Deficiency	Thyroid
Myxaedema	Thyroxine	Deficiency	Thyroid
Exophthalamic goitre	Thyroxine	Excess	Thyroid
Tetani	Parathyroid	Deficiency	Parathyroid
Plummer’s disease	Thyroxine	Excess	Thyroid
Addison’s disease	Mineralocorticoids	Deficiency	Adrenal cortex
Conn’s disease	Mineralocorticoids	Excess	Adrenal cortex
Cushing’s disease	Corticosteroid	Excess	Adrenal cortex
Diabetes mellitus	Insulin	Deficiency	Pancrease
Myasthenia gravis	Thymosine	Excess	Thymus

Local hormones pheromones and insect endocrine glands

Local hormones : Hormones described so far are called circulating hormones, because these circulate in whole body with blood. When stimulated by physical or chemical stimuli, all body cells, except red blood corpuscles (RBCs), secrete certain such compounds which transmit coded informations of metabolic adjustments between neighbouring cells and hence remain ECF instead of diffusing into the blood. These compounds are called local tissue hormones or These are short-lived, because various enzymes present in ECF continue degrading these at a fast rate.

Local hormones are of two main categories-paracrine and autocrine. Paracrine hormones affect metabolism of cells located in the neighbourhood of those which secrete them. Autocrine hormones affect metabolism of the every cells which secrete them. Most local hormones are paracrine. These belong to the following categories :

Eicosanoids : These are a category of lipids derived from a fatty acid, arachidonic acid, synthesized in the plasma membrane of cells, and released in ECF. These are of four categories, viz. Prostaglandins, prostacyclins, thromoboxanes and
- Prostaglandins (PGs) : In 1935, Ulf von Euler discovered that human semen contains a very active compound presumably secreted by prostate gland and, hence, named as He found that after the semen is discharged in woman’s vagina, this compound contracts uterine muscles to facilitate the sperms to ascend into fallopian tubes and reach ova to fertilize these.
- Prostacyclins : These are found in walls of blood vessels and induce vasodilation. These also facilitate flow of blood in vessels and prevent thrombosis by inhibiting aggregation of
- Thromboxanes : These are secreted by blood platelets. These help in blood clotting by instigating aggregation of platelets at the place of These also instigate vasoconstriction at places of injury to prevent excessive loss of blood.
- Leukotrienes : These are secreted by eiosinophils of blood and mast cells of connective These serve as mediators in inflammatory and allergic reactions, induce bronchoconstriction (constriction of bronchioles), constrict arterioles and induce migration of neutrophils and eosinophils towards the places of inflammation. These can cause asthma, arthrites, colitis, etc.
Neuroregulators : These are a category of proteins which function as paracrine hormones in nervous These can be classified in three categories as follows :
- Neurotransmitters : These are synthesized in nerve cells and are secreted by exocytosis by axon terminals of these cells. These serve to transmit nerve impulses from one neuron to other neighbouring neurons, or muscles, or glands across synapses. About 60 to these have so far been discovered, but the most common of these are acetylcholine, norepinephrine, dopamine, serotonin and
- Neuromodulators : In nervous tissues, the neurons secrete such paracrine hormones which modulate (increase or decrease) the excitability of other neighbouring neurons. These hormones are called neuromodulators. The main positive neuromodulators which increase the excitability of other neurons are the amino acids glutamate and aspartate, and polypeptide named ‘P’ substance. Contrarily, the main negative modulators which decrease the excitability of neighbouring neurons are the amino acid glycine and gama aminobutyric acid (GABA), polypeptides named enkephalins, endorphins, dynorphins and tachychinins, and the nitric oxide (NO).

Nerve growth factors : The supporting glial cells of nervous tissues and cells of muscles, salivary glands and many other tissues secrete such polypeptide paracrine hormones which play important role in growth, development and survival of nerve That is why, these hormones are collectively called neurotrophins.

Pheromones : These are defined as chemicals excreted or released by one animal to the exterior, but evoke a physiological or behavioral response in another animal of the same species. Some pheromones, release on body surface, evoke a response in the recipient when tasted by the latter by licking, but most pheromones are volatile and odorous fatty acids (hydrocarbons) whose air borne molecules are received by recipient animals through olfaction. Certain insect pheromones are well-known examples. For instance, certain insects secrete bombykol or gyplure to attract their mating partners. Some other insects release geranoil to transmit information of food souirce of danger to their

In mammals, presumably including humans, certain volatile fatty acids secreted in vaginal fluid by females acts as pheromones. These may evoke sex drive in males, or affect menstrual cycle in other females. It has been observed that there is a tendency of synchronized menstrual cycles in female roommates. This “dormitory effect” must be due to pheromones.

Types of pheromones

Type	Example
(1) Sex pheromones	Bombycol – sillkmoth Queen substance – Honey bee Civetone – Cat Muskone – Muskdeer
(2) Aggregation pheromones	Geradiol – Honey bee
(3) Alarm pheromones	Danger signals
(4) Marking pheromones	Mark the territory in wild animals

Insect endocrine glands : The endocrine system of cockroach comprises intercerebral gland cells, corpora cardiaca, corpora allata, and prothoracic
Intercerebral gland cells : These cells lie in the brain between the two cerebral ganglia. They secrete a hormone called the brain This hormone activates the prothoracic glands to secrete their hormone.
Corpora cardiaca : These are a pair of rod- like bodies situated on the sides of the oesophagus just behind the brain. They secrete a growth
Corpora Allata : These are a pair of small,

FRONTAL GANGLION

PHARYNX

CORPUS CARDIACUM HYPOCEREBRAL

GANGLION

OESOPHAGEAL NERVE

VISCERAL GANGLION

BRAIN

FRONTAL NERVE FRONTAL CONNECTIVE

RECURRENT NERVE OESOPHAGUS

CORPUS ALLATUM

PROTHORACIC GLAND

CROP

GIZZARD

rounded bodies lying close behibnd the corpora cardiaca. They secrete a juvenile hormone in the nymphal stages. This hormone causes retention of the

PROVENTRICULAR GANGLION

Fig. – Endocrine glands of cockroach

nymphal characters and checks the appearance of adult characters. In other words, it keep the insect young, hence its name. In the last nymphal form, corpora allata become inactive, thereby resulting in the absence of juvenile hormone. The absence of this hormone permits the appearance of adult features. In the adult, the corpora allata again become active and secrete a gonadotropic hormone, which regulates egg production and development and functioning of the accessory sex glands.

Prothoracic glands : These are fairly large, irregular glands situated in the prothorax. They secrete a hormone called ecdyson, which controls moulting of the nymphs. The prothoracic glands degenerate after

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Hormones and their mechanism

(i) Properties of hormones

(ii) Classification of hormones

(b) On the basis of mode of action

(a) Negative feedback control

(2) Functions of some important hormones

(3) Number of hormones secreted by different endocrine glands

Pituitary Gland (Hypophysis)

Parts and component

(2) Neurohypophysis

Posterior lobe

(a) Somatotropin (STH) or Growth Hormone (GH)

(3) Effects of hyposecretion of growth hormone

(4) Effects of hypersecretion of growth hormone (N P)

Effect of vasopressin

Hypothalamus

Important tips

Thyroid gland

(v) Synthesis and secretion of iodinated hormones

(vii) Irregularities of thyroid gland

(4) Plummer’s disease or Toxic Adenoma : It is

Parathyroid gland

(iii) Irregularities of parathormones

(b) Hyperparathyroidism (Hypersecretion of parathormone) :

Adrenal gland

(a) Function of epinephrine

Significance of adrenal medullary hormones

(iv) Effects of irregularities of adrenal secretion

Pancreas

Thymus gland

(iii) Function of thymus glands

Pineal gland (Epiphysis)

Gonads

(i) Testes

(b) Function

Hormonal sexual abnormalities

Hormonal Contraception

Gastro-intestinal mucosa placenta skin, kidney and heart

Local hormones pheromones and insect endocrine glands

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