Endocrine Glands and Hormones

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 homeostasis. So both are collectively form neuro-endocrine system. The study of these two systems is called neuro-endocrinology. 

Glands of body : Animals have three types of glands.

(i) Exocrine gland (Gr., ex = out + krinein = to secrete) : These glands have ducts for discharging their secretions. Therefore, they called duct glands. ex – Liver, Sweat gland, Sebaceous gland, Gastric glands and some intestinal glands.

(ii) 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.

(iii) Heterocrine glands : These glands consist of both exocrine and endocrine tissue. The exocrine discharge its secretion by a duct and the endocrine tissue discharges its secretion into the blood. Pancreas and gonads are heterocrine glands. These are also called mixed glands.

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.

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

Term hormone was coined by starling (1905) from Greek word Homone means to excite. It is a mishomer because a number of hormones are known to have inhibitory effect (e.g., Somatostatin).

General function of hormones

(1) Some hormones control Basic Metabolic Rate (BMR) e.g., thyroxine of thyroid gland.

(2) Some hormones control the secretion of other endocrine glands, e.g., Tropic hormones of Anterior pituitary control Thyroid, Adrenal cortex, gonads, etc. 

(3) Some hormone control blood pressure e.g., Aldosterone, Atrial Natriuretic Hormone (ANH) of heart, Vasopressin or ADH’, oxytocin and Renin of kidney.

(4) Increase production of RBC e.g., erythropoietin of kidney.

Properties of hormones

(1) These are secreted by endocrine gland (biogenic in origin).

(2) Their secretions is released directly into blood (except local hormones e.g., gastrin).

(3) These are carried to distantly located specific organs, called target organ.

(4) These have specific physiological action (excitatory or inhibitory). These co-ordinate different physical, mental and metabolic activities and maintain homeostasis.

(5) The hormones have low molecular weight e.g., ADH has a molecular weight of 600� daltons.

(6) These act in very low concentration e.g., around 10^� molar.

(7) Hormones are non antigenic.

(8) These are mostly short-lived. So have a no cumulative effect.

(9) Some hormones are quick acting e.g., adrenalin, while some acting slowly e.g., oestrogen of ovary.

(10) Some hormones secreted in inactive form called Prohormone e.g., Pro-insulin.

(11) Hormones are specific. 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.

(12) Hormones after their action destroyed in liver and kidney.

Classification of hormones

(1) On the basis of chemical nature : On the basis of chemical composition hormones are classified into three categories.

(i) Amine hormones : These are derived form tyrosine amino acid and have amino $\left(-N{H}_2\right)$ group e.g., Thyroxine, Epinephrine, Nor-epinephrine.

(ii) Steroids : These are fat soluble and have sterol group. These are derived from cholesterol e.g., hormones of adrenal cortex (cortisol, cortisone, corticosterone, aldosterone) testes (testosterone) and ovaries (estrone, estradiol, progesterone etc.)

(iii) Proteinous and peptide hormones : These are formed of 3 – 200 amino acids interlinked by peptide bonds and are water soluble e.g.,

(a) Proteinous hormones like STH, TSH, FSH, LH etc. Out of these FSH and LH are glycoproteins.

(b) Long peptide hormones like insulin and glucagon, ACTH, Paratharmone.

(c) Short peptide hormones like oxytocin, ADH, MSH. These hormones formed of a few amino acids.

(2) On the basis of mode of action

(i) 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 sized. Hormone receptor complex activates a membrane enzyme adenyl cyclase which hydrolyse ATP into cyclic AMP. Which acts as secondary messenger, c-AMP activates an inactive enzyme system by cascade effect. So their mode of action is called second messenger hypothesis. e.g., These includes proteinous, peptide and amine hormones.

(ii) Delayed acting hormones : These hormones initiate response after some time. These are small sized so are diffusable through the plasma membrane of their target cell. 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.

Release of hormones : Hormones are released from endocrine glands by three types of stimuli.

(1) Specific metabolic : The presence of a specific metabolite in the blood elicits the hormone to deal with it. For instance excess of glucose in the blood causes the release of insulin from the pancreas and decrease of glucose in blood causes the release of glucagon from pancreas.

(2) Other hormone : The presence of a specific hormone in the blood induces the release of another hormone. For example TSH stimulate thyroid gland to release thyroxine hormone and ACTH stimulate Adrenal cortex to release their hormones.

(3) 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 danger.

Mechanism of hormone action : The hormones act in two ways –

(1) 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 cell. 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 –

(i) Formation of cAMP : Mechanism of formation of cAMP was discovered by E.W. Sutherland in 1950. The hormone receptor complex causes the release of an enzyme adenylcyclase. 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.

(ii) 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⁺ etc. 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.

(2) Within a cell : The steroid hormones act within the cell. 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 body. 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.

(1) Negative feedback control

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

(2) Positive feedback control : Oxytocin released by posterior pituitary gland stimulate contraction of uterus during child birth. As the contraction of uterus progresses, more and more of oxytocin is released. This is called positive feed back control.

Discovery & Terms

(1) Term &aposendocrine&apos was first used by Bernard.

(2) Thomas Addison is called as father of endocrinology.

(3) Walter canon stated that the hormones maintain homeostasis in the body.

(4) Von Euler coined the term &aposprostaglandin&apos

(5) Kendall for the first time prepared the crystals of thyroxine.

(6) Harrington and Barger studied the molecular structure of thyroxine.

(7) Term &aposthyroxine&apos was coined by Whartson.

(8) Sutherland discovered cAMP.

(9) Parathormone was first isolated by Collip.

(10) Potts discovered the structure of PTH.

(11) Axelord studied the structure of epinephrin and nor-epinephrin.

(12) Endocrine structures of the pancreas were discovered by langerhans.

(13) Structure of insulin was studied by Sanger. He was given Nobel prize in 1958. He was rewarded Nobel prize in 1980 for gene structure.

(14) Human insulin was synthesized by Tsan.

(15) Glucagon was discovered by Kimball and Murlin.

(16) Term &apos Secretin&apos was coined by Beylis and Starling.

(17) Adrenal gland was discovered by Eustachian.

Pituitary Gland (Hypophysis)

Pituitary 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 of 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, hypophyseal fossa of the sella turcica of sphenoid bone. It is connected by a short stalk called Infundibulum, to the ventral wall (Hypothalamus) of diencephalon. That is why it is also called hypophysis cerebri. It weight about 0.5 to 1 gm. It control 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

Neurohypophysis

Structure of pituitary gland : Pituitary gland is comprised of two main lobes – Adenohypophysis and Neurohypophysis. Adenohypophysis is arises as hypophysial or Rathke&aposs 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.

In pituitary following types of cells are found :

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

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

(i) Acidophils : It is also known as a-cells synthesize and secretes growth hormone and prolactin.

(ii) Basophils : It is also known as cyanophils or $\beta$-cells synthesize and secretes TSH, ACTH, FSH, LH and MSH hormones.

(3) Pituicyte cells : These cells found in neurohypophysis of pituitary. These are supporting neuroglia cells and gives support to herring bodies.

(4) Herring bodies : Herring bodies Are dilated terminal portion of Neurosecretory axon constituting hypothalamohypophyseal tract. They are hormone precursors for oxytocin and vasopressin.

Blood supply to pituitary or Hypophyseal portal system : A pair of posterior hypophysial arteries and a pair of anterior hypophysial arteries provide blood to the 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 by means of a "circle of willis". The anterior hypophysial artery which bring blood into this circle big ureates 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. Then 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. Hypothalamic hormone reached anterior pituitary by portal system.

Hormones of adenohypophysis

Adenohypophysis secretes seven hormones which are proteinous in nature. These hormones controlled by the controlling factors. Secreted by the hypothalamus. These are 9 main controlling factors. Out of them 7 are releasing factors (RF) and 3 are inhibiting factor (IF). Complete failure of adenohypophysis (ant. pituitary) is leads to simmonds syndrome. Hormones that influence another endocrine gland are called tropic or tropin hormones. The FSH/LH regulate Testes and ovaries, thyrotropin stimulate thyroid, whereas corticotropin act on cortex of adrenal gland. Various hormones of adenohypophysis are as follows -

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

(i) Functions of growth hormone : Molecules of this hormone are polypeptides of 191 amino acid monomers. 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.

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.

(ii) 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.

(iii) Effects of hyposecretion of growth hormone

(a) Nanism or ateliosis : Hyposecretion (undersecretion) of growth hormone is childhood results into a blunted growth of body. 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.

(b) Midgets : Unlike the thyroid cretinism, the development of brain is normal in pituitary dwarfs, but like thyroid cretinism, the pituitary dwarfs are also infertile. The dwarfs of circuses are pituitary dwarfs. these are called midgets.

(c) Pituitary myxoedema : 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 myxoedema. 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 disability. Hence, the person becomes disheartened.

(iv) Effects of hypersecretion of growth hormone

(a) Proportionate gigantism : Hypersecretion (oversecretion of growth hormone during growth period (childhood and adolescence) causes excessive growth (hypergrowth) of all body parts, resulting into a symmetrically giant body. This is called proportionate gigantism.

(b) Disproportionate gigantism or acromegaly : The concerned person may attain a height of 8 feet or ever more.

Oversecretion of growth hormone after growth period also causes gigantism, but in this the long bones do not grow in length due to closed epiphyseal plate 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 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.

(c) Kyphosis : In some cases, the backbone bends and thickens, causing hunchback condition (kyphosis). Breasts enlarge and mammary gland may yield milk. The patients often complain of headache, sexual disorders, muscular pain, and impaired vision and memory.

(d) Hypersecretion of growth hormone raises blood glucose level (hyperglycemia) which may cause diabetes mellitus.

(e) Ketosis : Increased breakdown of fat may release ketone bodies, mainly acetoacetic acid, in blood, causing ketosis.

(2) 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 hypothalamus. 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. Prolactin levels rises during pregnancy due to PRH of hypothalamus.

Hypersecretion : (i) Prolactin hormone is secreted both in males as well females. In males it influence sexual behaviour. Its hypersecretion may hinder menstruation.

(ii) May cause impotency

(iii) In pigeons and doves, it stimulates the epithelial cells of crop in both males and females to secrete "pigeon milk" for nutrition of newly hatched infants.

(3) Follicle-stimulating hormone (FSH) or Gametokinetic factor : It is a glycoprotein whose molecules consists of a polypeptide of 204 amino acid residues. 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. GnRH (gonadotropin-releasing hormones) from hypothalamus stimulats FSH release. There is no gonadotropin inhibing hormone. 

(4) Luteininzing hormone (LH), or Interstitial cell-stimulating hormone (ICSH) : This is also a glycoprotein whose molecules contain a polypeptide of 204 amino acid residues. 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. Secretion of LH, like that of FSH is controlled by gonadotropin-releasing hormone (GnRH).

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 activates 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 are also regulated by a "Clock", located hypothalamus. Further, the secretion of FSH in women are 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 antagonists are now used to respectively activate or retard the activities of gonads.

(5) Adrenocorticotropin or Adrenocorticotropic hormone (ACTH) : It is secreted by corticotroph cells of anterior pituitary. 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.

(6) 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 gland. 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. There is no thyrotropin-inhibiting hormone.

(7) 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 remnant cells of this lobe, which become a part of pars distalis. Its molecule is a small peptide of 13 amino acid residues. Its secretion is controlled by hypothalamic hormones, viz MRH (Melanocyte releasing hormone) and MIH (Possibly oxytocin is released at this time by posterior pituitary of both mother and the fetus. At actual Melanocyte inhibiting hormone). In lower vertebrates, the target cells of this hormone are the melanophores. Melanin is antagonistic to melanocyte stimulating hormone MSH affects spreading of the melanin granules in these cells so that skin colour darkens in fish and amphibian but in birds and mammals of the role of MSH in uncertain. In man, presence of MSH receptor in brain suggests its may influence brain activity.

(8) Metabolic hormone (MH) : It influence carbohydrate and fat metabolism of body. The hormone which influence carbohydrate metabolism is known as diabetogenic hormone. The hormone which influence fat metabolism is known as ketogenic hormone.

Hormones of neurohypophysis and their functions

The herring 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 proteinous in nature.

(1) 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 an "osmoregulatory centre" located in hypothalamus. Another effect of vasopressin is to increase blood pressure by contracting blood vessels (vasoconstriction) in several tissues hence the name vasopressin.

Effect of vasopressin

(i) Vasoconstriction of the blood vessels of skin by this hormone retards secretion of sweat glands.

(ii) It also stimulates contraction of intestinal smooth muscles.

(iii) When vasopressin is released in excessive amounts, the urine becomes concentrated and blood is diluted, increasing BP. The osmo-regulatory centre, then, issues motor impulses to check release of vasopressin.

(iv) 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 BP.

(v) In acute diuresis, quantity of urine may increase to about 20 litres instead of normal 1 to 2 litres per day. This condition is called polyurea or diabetes insipidus (passing of water tasteless urine). It causes dehydration of body and thirst.

(2) 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 pregnancy. As the sensory impulse of increasing labour pain reaches hypothalamus, more and more oxytocin is released from posterior pituitary under a positive feedback regulationchildbirth, 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.

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 cells. 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 adenohypophysis. These neurohormones are proteinous in nature and formed of 3 – 20 amino acids.

Hypothalamo – pituitary complex : Pituitary gland is closely related with hypothalamus. 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.

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&aposs apple) and a few anteriomost tracheal rings. It is a dark brown and H-shaped/butterfly bilobed gland.

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 endocrine. 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&aposs average weight is 30 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, 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.

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 &aposC&apos 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 exocytosis. Each molecule of thyroglobulin contains about 500 amino acid momoners of which 123 monomers are of tyrosine at fixed places. 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, forming 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 colloid, 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 of the same or different molecules of iodothyroglobulin. It results in the formation of several groups of਌omplexes of tetraiodothyronine (thyroxine – T₄) and some of triiodothyronine (T₃) in the colloid. Each T₄ complex obviously contains two tyrosine 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.

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.

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 150$\mu$g of iodine from food. We can obtain this from dairy 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. Peroxidase continuosly oxidizes iodide ions into molecular iodine (2I^–$\to$I₂). Iodine is, then, released by follicular cells into follicular cavity.

Hormones of thyroid

Thyroid gland secretes two iodinated hormones. Thyroxine (T₄) and Tri iodothyronine (T₃) and one non iodinated hormone thyrocalcitonin. Secretion of thyroid gland is regulated by TSH of anterior pituitary lobe. Thyroxine was first isolated by Kocher (1914) but was first crystalized by Kendall (1919). Its molecular structure was given by Harrington and Berger (1927). They also synthesized thyroxine.

(1) Thyroxine : It is an iodine containing (6% iodine) amine hormone which is derived from tyrosine amino acid. 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 :

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

(ii) In 1912 Gudernatsch discovered that metamorphosis in frog&aposs 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 metamorphosis.

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 paedogenesis. The paedogenetic larvae of Ambystoma are called Axolotl larvae.

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

(iii) Functions of osmo-regulation and regulation of moulting have been ascribed to these thyroid hormones in cold-blooded vertebrates (fishes, amphibians and reptiles).

(iv) These control working by renal tubules of kidney so control urine output.

(v) These help in homeothermy in warm blooded animals.

(vi) Synthesis of additional sodiumpotassium pump (Na⁺/K⁺ ATPase), which then use more ATP more heat is given off, and body temperature rises. This phenomenon is called calorigenic effect of thyroid hormone, and thus maintain normal body temperature.

(2) Thyrocalcitonin (TCT) : It is a long peptide hormone secreted by parafollicular cells of thyroid gland (C-cells). It&aposs secretion is regulated by increased plasma level of calcium by feedback mechanism. TCT lower calcium 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.

Irregularities of thyroid gland

(1) Hypothyroidism : (Decreased secretion of thyroxine from thyroid gland). It leads to the following diseases –      

(i) Cretinism : It is disease of infants, called cretins. It is characterised by Decreased BMR (50% than normal) stunted growth retarded mental development so low I.Q., delayed puberty decreased body temperature, heart rate, pulse rate, blood pressure and cardiac output reduced urine output decreased sugar level in blood, pigeon&aposs chest (chest bulging forward in sternal region). Cretinism can be congenital (absence of thyroid due to genetic defect) or endemic (absence of iodine in diet). It can be corrected by thyroxin administration.

(ii) Myxoedema : It occurs due to deficiency of thyroxine in adults like cretinism, 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 tissue. It can also be corrected by thyroxine administration.

(iii) Endemic or simple goitre or colloid goitre : It occurs due to deficiency of iodine in drinking water. 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.

(iv) Hashimoto&aposs 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 gland.

(2) 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 mitochondria. 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, insomnia, 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.

(i) Simple goitre : Hyperthyroidism may be simply because of overactive cells of a normal gland, or because of an enlargement of the gland, causing goitre.

(ii) 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 patient. Protrusion of eyeballs is due to accumulation of mucus in eye orbits.

(iii) Grave’s or Basedow&aposs disease : Enlargement of the gland is usually due to a diffused growth.

(iv) Plummer&aposs disease or Toxic Adenoma : It is due to formation of one or more hypersecretoy nodules plummer&aposs diseases or Toxic Adenoma in the gland.

Parathyroid gland 

(1) Position and structure : These are four in number which are wholly or partially embedded in the dorsal surface of the thyroid gland two glands in each lobe of thyroid gland. Each is oval shaped, small sized (5൵ 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.

(2) Hormones of parathyroid : Active hormone secreted by parathyroids is parathormone (PTH), also called Collip&aposs Hormone (Phillips collip, 1925). It was discovered and purified by Collip in 1925. Its crystals were 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 &aposhomeostasis&apos 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.

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⁺.

Irregularities of parathormones

(1) Hypoparathyroidism (Hyposecretion of parathormone)

(i) 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 trembling.

(ii) 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).

(iii) Childhood hypoparthyroidism retards growth, particularly of bones, teeth, hair and brain. Vitamin D is administered to such children.

(2) Hyperparathyroidism (Hypersecretion of parathormone) 

(i) Osteoporosis : Oversecretion of parathormone is rare and occurs usually due to overgrowth of one or more parathyroid glands. It causes demineralization of bones which, therefore, become soft, weak, distorted and fragile. This is called osteoporosis.

(ii) 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 weakened.

(iii) 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 operation.

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 or superior 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. Like thyroid, adrenals also highly vascular in nature.

Structure : Each adrenal is a small ( 5 cm long, 3 cm broad and 1 cm thick), triangular and yellowish cap like structure. Its weight in humans is about 3.5 to 5.09 gm. At birth Adrenal gland best developed. Each gland has two parts – Outer cortex and inner medulla.

(1) Outer cortex : The cortex is derived from mesoderm and forms about 80% part of the gland. Cortex consists of fatty, cholesterol rich cells. These cells distinguish the cortex into three zones or regions.

(i) Zona glomerulosa : It is the outer part of the cortex (15% of the gland), which consists of small polyhedral cells. It secrets mineralocorticoids e.g., Aldosterone.

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

(iii) 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 anastomosing network. It secrets sex hormones.

(2) Inner medulla : The medulla is derived from ectoderm and forms about 20% part of the gland. 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

About 20 steroids (steroidogenic) compounds have secreted from adrenal cortex. These are called adrenocorticoids (corticosteroids). Only few of them are biologically active as hormone. These hormones are steroid in nature. The later, however account about 80% of the secretion of adrenal cortex and are classified into three categories.

(1) 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 urine. 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 promoting reabsorption of HCO^–₃ and regulating excretion of H⁺ by kidneys. It also promotes absorption of water and salt in intestine, mainly in colon. The Renin-angiotensin-aldosterone or RAA pathway controls secretion of Aldosterone.

(2) Gluco-corticoids : These include three main hormones – cortisol, corticosterone and cortisone. Cortisol is most abundant (about 95%) and most important. These hormones play an important role in carbodydrate, fat and protein metabolism as follows –

(i) Cortisol retards glucose consumption and protein synthesis, but promotes breakdown of proteins and fats in the cells.

(ii) Effects of glucocorticoids upon liver are anabolic. These promote 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.

(iii) 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 effect. It also denotes 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.

(iv) 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 inhibited. 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.

(v) Cortisol increases RBC count, but decreases the WBC count of blood. It also elevates blood pressure (BP).

Sex hormones : The zona reticularis of adrenal cortex secrets androgen and estrogen in small quantity. 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 body. 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.

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 gland. 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.

Secretion of mineralocorticoids 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.

Hormones of adrenal medulla

The chromaffin cells of adrenal medulla synthesize two hormones adrenalin or epinephrine (80%) and nor-adrenalin or nor-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 norepinephrine. Epinephrine is derived by methylation of norepinephrine.

$\text{Tyrosine }\underset{\text{Decarboxylation}}{\stackrel{\text{Hydroxylation}}{\to }}\text{Dopamine }\stackrel{\text{Hydroxylation}}{\to }$

$\text{Nor epinephrine }\stackrel{\text{Methylation}}{\to }\text{ Epinephrine}$

Cortisol from adrenal cortex induce synthesis of enzymes needed to convert nor epinephrine to epinephrine. Norepinephrine lacks the converting enzymes. Because the ANS controls the chromaffin cells directly, hormones release can occur very quickly.   

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.

Function of epinephrine

(1) 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.

(2) Reduced supply of blood causes a pale skin (pallor), but arrector pilli muscles of skin contract, causing gooseflesh.

(3) Mouth becomes dry due to poor secretion of saliva.

(4) 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 glands.

(5) Kidneys produce small volume of urine, and muscles or urinary bladder relax.

(6) In pregnant women, the muscles of uterus contract, increasing the possibility of abortion.

(7) 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 reaction. Obviously, the blood pressure, increased due to effect of norepinephrine, is reduced to some extent.

(8) Pupils dilate due to contraction of radial dilatory muscles of iris. Secretion of tear by lacrimal glands increases.

(9) Epinephrine causes relaxation of the smooth muscles of trachea, bronchi and bronchioles. These organs, therefore dilate, so that breathing becomes easier and faster. Remember that epinephrine is used in treatment of asthma for this reason.

(10) Contractions of cardiac muscles intensify, increasing both rate and force of heartbeat, pulse rate, arterial pressure and cardiac output.

(11) Due to an increase in adhesiveness of blood platelets, the time of blood clotting is considerably reduced.

(12) The spleen contracts, releasing its reserve of blood corpuscles whose number in blood, therefore, increases.

(13) In islets of Langerhans in pancreas, secretion of insulin hormone decreases, but that of glucagon increases. Glucagon causes glycogenolysis, i.e. breakdown of glycogen into glucose in liver and skeletal muscles.

(14) 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 irritable.

(15) External genitalia become flaccid, but ejaculation becomes early and forceful.

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.

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".

Effects of irregularities of adrenal secretion

(1) Hyposecretion : This may be a genetic defect. Undersecretion of adrenocorticoids (hypocorticism) causes Addison&aposs disease which is relatively rare and occurs in both men and women between the ages of 20 to 40 years. This disease was first described by Thomas Addison in 1849, 1855. It is maintained in following symptoms :

(i) Owing to low aldosterone and gluco-corticoides 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, etc.

(ii) Owing to low cortisol level, glucose level also falls in blood (hypoglycemia). This sharply reduces BMR in body cells. 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.

(iii) Decreased cortisol level induces gastro-intestinal disorders, resulting in loss of appetite, nausea, vomiting, diarrhoea, abdominal pain and restlessness.

(iv) Due to a sharp decline in body&aposs chemical defense and resistance, sensitivity to cold, heat, infection, poisoning and other adverse condition increases. 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.

(v) Addison&aposs disease also causes an increase in the number of WBCs, resulting into eosinophilia, lymphocytosis, leucocytosis, etc.

(vi) Undersecretion of sex hormones causes impotence in males and disorders of menstrual cycle in females.

(vii) 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 parts.

(viii) As increase in H⁺ concentration in blood may cause acidosis.

(2) Hypersecretion : Oversecretion of adrenocorticoids (hypercorticism) causes following disorders and diseases –

(i) Glucose level rises in blood (hyperglycemia). This may lead to diabetes mellitus.

(ii) Irregular deposits of fat, particularly in thoracic parts and face, imparts asymmetrical shape to the body. 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&aposs disease (Cushing, 1932). Patients may die from brain haemorrhage, cardiac arrest, pneumonia, etc.

(iii) Retention of sodium and water is the ECF increases blood pressure, causing severe hypertension and associated symptoms like severe headache.

(iv) 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 (nocturia), etc. Similarly, excessive loss of H⁺ in urine may cause alkalosis.

(v) Excessive mobilization of materials from all parts of body had widespread deteriorating effects. For instance, mobilization of proteins from all cells causes tissue wasting. similarly, mobilization from bones renders the bones weak and fragile (osteoporosis).

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

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

Pancreas

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

Structure : About 99% part of the gland is exocrine and formed of hollow pancreatic acini or lobules embedded in a 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).

Cells Types in the Pancreatic Islets

Each pancreatic islet includes four types of hormone-secreting cells :

(1) Alpha or A cells constitute about 15% of pancreatic islet cells and secrete glucagon.

(2) Beta or B cells constitute about 80% of pancreatic islet cells and secrete insulin.

(3) Delta or D cells : It’s constitute about 5% of pancreatic islet cells and secrete somatostatin (identical to growth hormone-inhibiting hormone secreted by the hypothalamus).

(4) F cells : It’s constitute the remainder of pancreatic islet cells and secrete pancreatic polypeptide.

Hormones of pancreas and their role

The $\beta$ and $\alpha$ cells of islets of Langerhans respectively secrete insulin and glucagon hormones which are important regulation of carbohydrate, protein and fat metabolism in the body.

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

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, $\alpha$ and $\beta$, 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.

(i) Hypoinsulinism : In insulin deficiency, body cells fail to obtain glucose from blood. 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 more than 200 mg/100 ml blood the person concerned suffers from diabetes mellitus in which the urine becomes sweet.

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 $\beta$-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.

(ii) 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 decline. 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.

(2) Glucagon : This is secreted by the alpha cells of islets of Langerhans. 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.

(3) Somatostatin and Pancreatic polypeptide : Modern physiologists have postulated that the $\delta$ and F (PP) cells of pancreas respectively secrete somatostatin (SS) and pancreatic polypeptide (PP). Somatostatin resembles the growth hormone inhibitory hormone (GHIH) secreted by hypothalamus. Its molecule is a small peptide of 14 amino acid residues. Acting as a paracrine hormone, it serves to retard secretory activities of $\alpha$a and $\beta$ 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.

Thymus gland

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

Structure : Structurally, it is like lymph gland enveloped by a thin, loose and fibrous connective tissue capsule. Septa, or trabeculae extending inwards from the capsule, divide the two lobes of the gland into a number of small lobules. 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&aposs corpuscles.

Function of thymus glands

(1) 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 lymphocytes.

(2) The major function of thymus is to secrete thymosin hormone, thymic humoral factor (THF), thymic factor (TF), thymopoietin. 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.

(3) 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 puberty. 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, (0.1 to 0.29) whitish and somewhat flattened ectodermal gland situated at the tip of a small, fibrous stalk that arises from dorsal wall of diencephalon, i.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. 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. Melatonin also is a potent antioxidant. Melatonin causes atrophy of gonads in several animals.

Gonads 

The gonads are the sex glands, the testes and the ovary. Testes is the male gonad and ovary is the female gonads. 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.

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 cholesterol. The main androgen is testosterone other less important androgens include androstenedione and dehydroepiandrosterone (DHEA). It is a masculinizing hormone. From puberty to the age of about twenty year i.e. adolescence or the period of sexual maturation or attainment of adult hood.

Function

(1) It stimulates the male reproductive system to grow to full size and become functional.

(2) It stimulates the formation of sperms (spermatogenesis) in the seminiferous tubules.

(3) 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, thickening of skin, deepening of voice, enlargement of larynx, broadening of shoulders, Narrow lips enlarged and stronger bones and muscles. It also maintains these characters.

(4) It also determines the male sexual behaviour sex urge, aggressive behaviour.  

(5) Under its effect protein anabolism increases. (This function is obvious in the heavier muscle and bone mass of most men as compared to women).

(6) Grythropoisis in bone marrow increases.

(7) In brief, testosterone determines libido or sex drive. 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.

(8) Increased sebaceous gland secretion.

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 embryo. 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 characteristics.

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 hormones. 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 relaxin. They derived from cholesterol.

(1) Estrogens : These are secreted by the cells of the Graffian (ovarian) follicle surrounding the maturing ovum in the ovary. 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. Graffian 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.

(2) Progesterone : It is secreted by the corpus luteum. The latter is a yellowish body formed in the empty Graffian 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.

(3) Relaxin : It is produced by the corpus luteum at the end of the gestation period. It relaxes the cervix of the uterus and ligaments of the pelvic girdle for easy birth of the young one.

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 flat. 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.

Progesterone : Also called anti-abortion hormone.

Gravidex test : Involve testing of hcG of placenta in the urine to test the pregnancy.

Contraceptive pills : Contain less oestrogens and more progesterone so called combined pills. 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 hormones.

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. 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