(i) 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.

(ii) 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.

# 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.

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 diencephalon. 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
# (1) Adenohypophysis
(i) Pars distalis
(ii) Pars tuberalis
(iii) Pars intermedia
# (2) Neurohypophysis
(i) Pars nervosa
(ii) Infundibulum

# Structure of pituitary gland : Pituitary gland is comprised of two main lobes – Adenohypophysis and Neurohypophysis. 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.

In pituitary following types of cells are found –
(1) Chromophase 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 -cells.
(ii) Basophils : It is also known as cyanophils.
(3) Pituecyte cells : These cells found in neurohypophysis of pituitary.
(4) Herring bodies : These are the bodies which store neurosecretory.

# Blood supply to pituitary : 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 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 nature. These hormones 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 adenohypophysis are as follows –

#(a) Somatotropin (STH) or Growth Hormone (GH)
- (1) 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. 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.

- (2) 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 age.

- (3) Effects of hyposecretion of growth hormone
(i) 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.
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.
(ii) 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.
(iii) 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 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 debility. Hence, the person becomes disheartened.

- (4) Effects of hypersecretion of growth hormone
(i) 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 body. This is called proportionate gigantism.
(ii) Disproportionate gignatism 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 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 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.
(iii) 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.
(iv) Diabetes mellitus : Hypersecretion of growth hormone raises blood glucose level (hyperglycemia) which may cause diabetes mellitus.
(v) Ketosis : Increased breakdown of fat may release ketone bodies, mainly acetoacetic acid, in blood, causing ketosis.

# (b) 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.

- (1) Hypersecretion : Prolactin hormone is secreted both in males as well females in males it influence sexual behaviour. Its hypersecretion may hinder menstruation.
- (2) Hyposecretion : May cause impotency. 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.
- (c) 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.
- (d) 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.

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.

# (e) 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.

# (f) 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.

# (g) 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 residues. 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.

# (h) 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 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.
- (a) 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 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
(1) Vasoconstriction of the blood vessels of skin by this hormone retards secretion of sweat glands.
(2) It also stimulates contraction of intestinal smooth muscles.
(3) 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.
(4) 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.
(5) 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.
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.

# (b) 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 pregnancy. 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".

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 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'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, 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 '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 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, 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 0.08mg of T4 and about .004mg 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g 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. Iodine is, then, released by follicular cells into follicular cavity.

# 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 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).

# (a) 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 :
(1) 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 body. 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.
(2) 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 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 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.
(3) Functions of osmo-regulation and regulation of moulting have been ascribed to these thyroid hormones in cold-blooded vertebrates (fishes, amphibians and reptiles).
(4) These control working by renal tubules of kidney so control urine output.
(5) These help in homeothermy in warm blooded animals.

# (b) 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.

# Irregularities of thyroid gland
- (a) Hypothyroidism : (Decreased section of thyroxine from thyroid gland). It leads to the following diseases :
(1) Cretirusm : It is disease of infants, called certin. 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'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.
(2) 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 tissue. It can also be corrected by thyroxine administration.
(3) 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.
(4) 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 gland.

- (b) 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, 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.

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

(2) 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.

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

# 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 gland. 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 1925. 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+.

# Irregularities of parathormones
- (a) Hypoparathyroidism (Hyposecretion of parathormone)
(1) 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.
(2) 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).
(3) Childhood hypoparthyroidism retards growth, particularly of bones, teeth, hair and brain. Vitamin D is administered to such children.

- (b) Hyperparathyroidism (Hypersecretion of parathormone) :
(1) 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 fragile. This is called osteoporosis.
(2) 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.
(3) 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 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 structure. Its weight in humans is about 4 to 6 gm. Each gland has two parts – Outer cortex and inner medulla.
(a) 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 present. Cortex consists of fatty, cholesterol rich cells. These cells distinguish the cortex into three zones or regions.
(1) 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.
(2) 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. Cartison, carticosterone.
(3) 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 network. It secrets sex hormones.
# 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 : Abut 20 steroids (steriodogenic) compounds have secreted from adrenal cortex. 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.
- (a) 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 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.
- (b) Gluco-corticoids : These include two main hormones – cortisol and carsicasterone. Cartisol is most abundant (about 95%) and most important. These hormones play an important role in carbodydrate, fat and protein metabolism as follows –
(1) 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, etc. Consequently, levels of glucose, FFAs and amino acids in blood pressure is elevated. This effect of cortisol in antagonistic to that of insulin.
(2) 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.
(3) 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 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.
(4) 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.
(5) 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 O2– 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 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. 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 norepinephrine. Epinephrine is derived by methylation of norepinephrine.

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.

# 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. 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.
(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.

- 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
- (a) 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 years. This disease was first discribed by Thomas Addison in 1849, 1855. It is maintained in following symptoms –
(1) 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, etc.
(2) 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.
(3) Decreased cortisol level induces gastro-intestinal disorders, resulting in loss of appetite, nausea, vomiting, diarrhoea, abdominal pain and restlessness.
(4) Due to a sharp decline in body's 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.
(5) Addison's disease also causes an increase in the number of WBCs, resulting into eosinophilia, lymphocytosis, leucocytosis, etc.
(6) Undersecretion of sex hormones causes impotence in males and disorders or menstrual cycle in females.
(7) 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.
(8) As increase in H+ concentration in blood may cause acidosis.

- (b) Hypersecretion : Oversecretion of adrenocorticoids (hypercorticism) causes following disorders and diseases –
(1) Glucose level rises in blood (hyperglycemia). This may lead to diabetes mellitus.
(2) 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's disease (Cushing, 1932). Patients may die from brain haemorrhage, cardiac arrest, pneumonia, etc.
(3) 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, etc.
(4) 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), etc. Similarly, excessive loss of H+ in urine may cause alkalosis.
(5) 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).
(6) 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.
(7) 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.)

# 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.

# Origin and position : The thymus gland is located in the upper part of the thorax near the heart. 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 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's corpuscles.

# Function of thymus glands
- (a) 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.
- (b) 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. 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.
- (c) 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.

# 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, 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.

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.

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. 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, deepening of voice, broadening of shoulders, 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.
(6) Grythropoisis in bone marrow increases.
(7) In brief, testosterone determines libido. 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 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. 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.

1. 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 origin.

# (a) 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 juice. It also stimulates the stomach movements.

# (b) 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 hormones.
(1) 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 stomach.
(2) Cholecystokinin-pancreozymin (CCK-PZ) : This hormone is secreted by the mucosa of entire small intestine. 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.
(3) Enterogastrone : It is secreted by the duodenal mucosa. It shows gastric contractions and stops the secretion of gastric juice.
(4) Enterocrinin : It is secreted by duodenal mucosa. It stimulates crypts of Lieberkuhn to secrete the enzymes in the intestinal juice.
(5) Duocrinin : It is secreted by the duodenal mucosa. It stimulates the release of viscous mucus from Brunner’s glands into the intestinal juice.
(6) Villikinin : It is secreted by the mucosa of the entire small intestine. It accelerates the movements of villi to quicken absorption of food.

2. Placenta : When the early embryo reaches into the uterus from fallopian tube, it becomes implanted with uterine wall by a placenta for support and nutrition. 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.

3. Skin : Vitamins of D group are synthesized in skin cells under the effect of ultraviolet (UV) rays of sunlight from cholesterol-derived compounds. 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.

4. 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 erythropoetin. 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.

5. 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 hormone. 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.