In this essay we will discuss about the hormones secreted by endocrine glands.
Hormones Secreted by Endocrine Glands
Essay Contents:
- Essay on the Introduction to the Hormones Secreted by Endocrine Glands
- Essay on the Nature of Endocrine Glands
- Essay on the Hormones Secreted by Thyroid Glands
- Essay on the Hormones Secreted by Parathyroid Gland
- Essay on the Hormones Secreted by Pituitary Gland
- Essay on the Hormones Secreted by Adrenal Gland
- Essay on the Hormones Secreted by Reproductive Glands
- Essay on the Hormones Secreted by Thymus
- Essay on the Hormones Secreted by Pineal Body
- Essay on the Gastrointestinal Hormones
Essay # 1. Introduction to the Hormones Secreted by Endocrine Glands:
The complexity of functions observed in vertebrates, especially mammals including man has been attained by the evolution of two integrating systems, the nervous system and endocrine system. The endocrine system maintains the volume and concentration of substances in the internal environment at constant level.
The endocrine system controls and integrates many body functions, including metabolism and energy balance, electrolyte metabolism and fluid volume regulation, growth and reproduction. Bayliss and Starling (1902) defined an endocrine gland as a ductless gland that synthesizes and then, upon appropriate stimulation, releases into the blood stream a chemical agent or hormone.
The hormone or the chemical messenger is carried by blood throughout the body of the animal to target cells which possess specific receptor sites for hormones. The receptor sites are present in the plasma membrane. Scharrer (1936) was the first to prove that neurohormonal secretion also plays a role in chemical regulation.
Chemically hormones may be divided into three groups steroids, polypeptides and amino acid derivatives. Endocrine glands do not possess a duct system, and each glandular cell has a surface that lies opposite to a capillary where diffusion can occur.
Secretion of the gland can be released directly into the extracellular fluid and circulation. Thus, hormones are released in the blood and can reach all tissues and cells, but act only on genetically differentiated cells of the body, the target cells.
The target cells possess specialized molecules for each hormone known as the receptors which are protein in nature and contain one or more sites to which the hormones can bind and mediate the specific cellular actions.
Some glands are composite in nature having both internal and external secretions e.g. pancreas, testes and ovaries. Some glands may be seasonal, being periodic and recurrent e.g. placenta and corpus luteum. These are provisional structures specially developed to preside over special occasions.
Essay # 2. Nature of Endocrine Glands:
Development of endocrine organs should not be regarded as a newly evolved one. It is just a modification of very old process. Metabolic activities are continuously going on in each and every cell of the body and the metabolites are coming out of the cell to exert some influence on the other cells —both near and distant —being carried through the blood stream.
The process of regulation through chemical messengers is the universal and probably the most primitive method of intercellular control. The metabolites which are of no use to the cells are poured in the blood stream or tissue fluid. This is the general rule. Endocrine glands are only a special development of the same principle in response to the organism’s requirement.
They evacuate certain useless metabolites and pour them directly into the tissue fluid just like carbon dioxide. These products finally enter the blood stream and exert influence on other tissues. That may be the explanation of these glands being ductless. The primitive unicellular organisms discharge their products of metabolic activities, directly into the surrounding water.
In the multicellular organisms, the cells still possess their primitive habit to discharge metabolites in the surrounding tissue fluid. Endocrine glands on the same tradition pour their secretions into the surrounding tissue fluid, from where they enter the blood stream like CO2 produced by the cells. The only difference is that CO2 is the general metabolite of all cells whereas hormone is a special metabolite of a few cells.
Essay # 3. Hormones Secreted by Thyroid Glands:
Thyrocalcitonin (TCT):
Harold H. Corp, a Canadian scientist in 1962 demonstrated the presence of TCT hormone in thyroid gland in addition to thyroxin.
TCT or calcitonin lowers the calcium level in the serum acting directly on bones and inhibiting the release of calcium. It’s secretion from thyroid is controlled by the calcium level of the serum.
The iodine binding capacity like that of the thyroid of higher vertebrates is also associated with the endostyle of Amphioxus, Ciona and Lampreys and dermal glands of hemichordates. Iodine binding appears to occur not uncommonly with the exoskeletal scleroproteins of many invertebrates.
In eels and certain fiat fishes, thyroid gland is concerned with metamorphosis and the gland’s secretion is controlled by the thyrotropin of pituitary. Despite the influences of the thyroid on teleost’s growth and development, there is till no decisive demonstration that in fishes the thyroid influences the basic metabolic rate. In fact, in cold-blooded animals, in general, reports from workers with various species indicate a variety of kinds of results.
Experiments involving thyroid administration to guppies and goldfish indicate that this hormone does not alter the rate of oxygen consumption, while oxygen consumption has been reported to increase in white grunts weighing more than 15 gms. Similarly, the administration of the hormone to tadpoles of Rana pipiens does not influence the O2 consumption, while it increases substantially in the adult condition.
Among the reptiles and birds, the effect of thyroid administration on the basal metabolic rate appears quite similar to that observed in mammals. In a few fishes thyroxin has been reported to be concerned with the regulation of liver glycogen and osmoregulation. In the stickleback, Gasterosteus, it increased thyroid activity which is responsible for their migration from salt to the fresh water during the breeding season. This change is subject to photoperiodic regulation.
Thyroid and Metamorphosis:
It was discovered long back that the feeding of thyroid gland material to amphibians hastens metamorphosis and, conversely, that removal of thyroid rudiments from the larval forms prevents metamorphosis. Metamorphosis can be obtained by administration of thyroxin in thyroidectomized individuals.
However, various amphibian species differ greatly in their responsiveness to thyroxin. During the early development none is responsive to this hormone, but most acquire the capacity at some particular stage of their development. The Mexican axolotl never responds to this metamorphism-inducing factor.
However, axolotl can be made to metamorphose by large doses of thyroxin. Other species, such as Necturus, never develops the reactivity and never metamorphoses. That the failure of metamorphosis in Necturus is the result of failure of tissue response rather than of the absence of appropriate thyroid principle is shown by the fact that Necturus thyroid would accelerate metamorphosis in Rana clamitans.
Control of Thyroid Secretion:
1. Role of Anterior Pituitary:
Control of thyroid secretion is predominantly by way of thyroid stimulating hormone (TSH). On the other hand, the circulating level of thyroxin controls the secretion of thyrotropic hormone. Rise of thyroxine level in blood depresses, while fall of thyroxine level accelerates secretion of TSH. In this way, the two hormones determine each other. In other words thyroid controls its own secretion through anterior pituitary.
2. Role of Hypothalamus:
Secretion of TSH is, in turn, regulated by the hypothalamus, presumably by a neuro-endocrine transmitted through the hypophysial portal system. The anterior-most region of the median eminence appears to be especially concerned.
3. Role of Environmental Temperature:
Cold climate stimulates and hot climate depresses the thyroid secretion and perhaps this is also a good mean for the heat regulation. This is perhaps through the reflex secretion of more TSH.
Synthesis and Release:
Iodide from food and water is absorbed by the small intestine and is concentrated by thyroid gland from the blood perfusing the gland. The uptake of iodide is influenced by thyroid stimulating hormone. In the microvilli of thyroid follicle cells, iodide is converted into free iodine (21– → I2 + 2E ) catalysed by the enzyme peroxidase.
The follicular cells synthesise a glycoprotein, thyroglobulin (M.W. 6,80,000) which passes into the colloid by the process of exocytosis. Free iodine becomes attached at the third position of the aminoacid tyrosine held to the thyroglobulin molecules by peptide bonds. This process results in the formation of monoiodotyrosine (MIT).
Further iodination at 5 position yields diiodotyrosine (DIT). Coupling of two molecules of DIT through ether linkage yields tetra iodo thyronine (DIT + DIT → T4 + alanine), while a molecule of DIT and a molecule of MIT form tri iodo thyronine (DIT + MIT → T3 + alanine). Iodinated thyroglobulin is stored in the lumen of the follicle as part of the colloid.
At the time of thyroxine secretion the thyroglobulin from the colloid is ingested by the microvilli and pseudopodia of thyroid follicular cells under the influence of TSH. Proteolytic degradation of thyroglobulin by lysosomes releases T4 and T3 together with amino acids, MIT and DIT. Deiodination of MIT and DIT results in iodide and tyrosine formation which may be recycled. Thyroxine (T4) and T3 diffuse into the blood (Fig. 1 & 2).
In blood 75% of thyroxine and T3 are bound to thyroxine binding globulin (TBG). 15% of thyroxine is bound of thyroxine binding prealbumin (TBPA) while the remaining 10% of thyroxine is transported by serum albumin. T3 does not bind to TBPA and thus 25% of T3 is transported by serum albumin.
Metabolism of Thyroid Hormone:
In plasma the free hormone is in equilibrium with protein bound hormone. Only 1/3000 of thyroxine is free. The free T4 and T3 enter liver and other target tissues where 80% is deiodinated. T4 on deiodination yields T3. The iodide, is recirculated to thyroid or excreted through urine.
Part of the T4 (1/3) is excreted through bile either in free form or in conjugated form with glucuronates or sulfates. From the gut part of the free or conjugated form is reabsorbed into the liver and part of it is eliminated through faecal matter. In case of T3, 80% is deiodinated and 20% is excreted through faeces (Fig. 3).
Physiological Actions of Thyroid Hormones:
Of the two thyroid hormones, T3 is considered to be the biologically active agent and T4 may be little more than a prohormone and a stable and regular source of supply of T3. T3 is three to five times more effective than T4. Its effects have early onset and are less protracted.
Calorigenesis:
Thyroxine and triiodothyronin increase oxygen consumption and heat production by the tissues of an organism, the main exceptions are brain, testes, spleen, uterus and anterior pituitary. As 90% of total oxygen consumption is by mitochondria, much attention has been focussed on the action of thyroid hormones on mitochondria.
It has been shown that thyroxine produces loose coupling of oxidative phosphorylation by increasing mitochondrial respiration and heat production without significantly reducing phosphorylation.
Protein synthesis is increased to provide mitochondrial electron carriers such as cytochrome C and cytochrome oxidase. T4 and T3 also exert a permissive effect on the weak calorigenic action of catecholamines, glucagon, glucocorticoids and growth hormone. T3 and T4 increase heat production by stimulation of sodium pump in cell membrane.
Carbohydrate Metabolism:
Thyroid hormones increase glucose mobilization and plasma glucose level by:
(a) Increasing intestinal absorption of glucose,
(b) Stimulation of glycogen breakdown in liver,
(c) Potentiating the glycogenolytic activity of hormones like adrenaline, and
(d) Stimulation of insulin breakdown. The entry of glucose into tissues like adipose tissue and muscle is promoted thus potentiating the hypoglycemic action of insulin.
Lipid Metabolism:
Thyroxine and T3 have a powerful lipolytic action on fat stores in tissues. The effect is direct as well as indirect through the potentiating effect on hormones like adrenaline, growth hormone, glucagon and glucocorticoids. The free fatty acids liberated are oxidized more rapidly yielding more energy. The level of plasma cholesterol is lowered.
Protein Metabolism:
Thyroid hormones are involved in the synthesis of specific proteins and maintain the normal rates of protein synthesis in general, by stimulating phosphorylation and the processes of translation and transcription.
Protein synthesis is severely depressed in hypothyroidism and excessive secretion of T4 and T3 results in protein break down, especially in. muscle leading to muscular weakness. Thyroid deficiency is associated with subcutaneous deposition of mucoprotein producing characteristic swelling (myxoedema).
Skeletal Growth and Development:
Thyroid hormones are essential for normal differentiation and maturation of fetal tissues. Deficiency may not result in reduction in fetal growth but skeletal and cerebral maturation are adversely affected. After birth, hypothyroidism produces reduced skeletal growth and development of all organ systems. Bone growth is retarded and dwarfism results. Infantile characters such as disproportionately short lower limbs and broad, flat nose are retained.
For the normal development of the central nervous system, during late embryonic and early post natal development, adequate levels of thyroid hormones are necessary. Deficiency leads to irreversible mental retardation (cretenism). In the absence of T4 and T3 myelination of nerve fiber tracts is defective. Blood supply to brain is reduced and, the size and number of neurons in cerebral cortex is reduced.
Blood Vascular System:
Thyroid hormones exert direct and indirect effects on heart and blood vessels by their potentiating action on the effects of adrenal hormones. In hyperthyroidism cardiac out put and heart rate are increased.
Besides these functions, thyroid hormones help in the conversion of β-carotene into vitamin A. In hyperthyroidism, thiamine and riboflavine requirements are increased.
Vitamin B12 absorption is influenced by thyroid hormones as hypothyroidism leads to megaloblastic type of anemia. Body heat regulation is also influenced by thyroid hormones as susceptibility to moderate cold is observed in hypothyroids. Lactation is stimulated by thyroxine.
Control of Thyroid Secretion:
Regulation of thyroid secretion is very important especially because of the delayed and prolonged action of the thyroid hormones. Fluctuations in the availability of the hormones are avoided as considerable amounts of the hormones are stored in the form of thyroglobulin in the gland and in bound form in the plasma.
Rate of synthesis of T4 and T3 is controlled within the gland itself so the hormone by Thyroid Stimulating Hormone (TSH). The secretion of the TSH is stiumulated by Thyrotropin Releasing Hormone (TRH) from the hypothalamus (Fig. 4).
TSH secretion is inhibited by T4 and T3 by a negative feedback mechanism. The secretion of TRH by hypothalamus is influenced by neural factors and feedback actions of TSH and T4 and T3.
TSH is a glycoprotein secreted by pituitary thyrotroph cells. It increases iodine uptake by the thyroid follicular cells, stimulates synthesis and release of T4 and T3. Cold promotes the synthesis of TSH through TRH. TRH is secreted by paraventricular, ventromedial and arcuate nuclei of the hypothalamus.
Antithyroid Drugs:
Certain drugs inhibit the thyroxine formation and hence are used for the treatment of Grave’s disease. These drugs block the iodine-concentrating mechanism and release whatever iodine the thyroxine has accumulated.
Thiourea, thiouracil and their substituted derivatives and propylthiouracil are such drugs which interfere with the organic incorporation of iodine by competing with tyrosine for the available activated iodine but allow iodide concentration.
Essay # 4. Hormones Secreted by Parathyroid Gland:
Four small oval parathyroids embedded in the posterior surface of the thyroid for a long time were confused with the thyroid itself. In man, each lobe measures 6 × 3 × 2 mm and the combined weight of the glands varies from 0.023 to 0.5 gm.
The active principle is parathyroid hormone or parathormone. Collip and Hanson prepared it from the gland by hydrolysing the gland tissue with 5% HQ. It is a polypeptide having a molecular weight 950.
Hormone Unit:
One U.S. Pharmacopoeia (USP) unit represents one-hundredth of the amount of parathyroid injection required to raise serum Ca of normal dogs. 1 mg. per 100 ml. of blood within 16 to 18 hours after administration.
It consists of a linear chain of 84 aminoacids. The biological activity appears to reside within the first 20 to 29 amino acids of the chain. The half-life of parathormone is about 18 minutes. It is rapidly degraded in circulation into small fragments.
Action of Parathormone:
Parathormone promotes increase in blood calcium concentration. Its main effects are on the bone, kidney and intestine.
Effect on Bone:
Parathormone stimulates the osteoclasts thereby promoting bone resorption. Calcium ions are freed from reserve skeletal depots and blood calcium level is maintained in case of hypocalcaemia. The dissolution of bone depends in part on the stimulation of lysosomal enzymes within the osteocytes and osteoclasts.
This results in the breakage of organic matrix of the bone, evident by increase in the excretion of hydroxyproline present in high concentration in collagen. Parathormone action on bone is very rapid and leads to decrease in pH due to increase in citrate and lactate production by tissues.
Effect on Kidney:
Dissolution of bone is accompanied by release of calcium and phosphate on administration of parathormone. Parathormone promotes the reabsorption of the calcium and depresses phosphate reabsorption by renal tubules. The lormone acts through cAMP and inhibits sodium reabsorption, and depression of phosphate reabsorption is a secondary effect.
The sodium in the tubule is reabsorbed distally but phosphate is excreted leading to pronounced phosphaturia, and fall in blood phosphate concentration. As calcium and phosphate have a solubility product relationship, the fall in blood phosphate necessitates increased entry of calcium from bone into blood. Thus, the actions of parathormone on bone and kidney lead to the hypercalcaemic effect of the hormone.
Effect on Intestine:
Parathormone increases the absorption of calcium from the intestine. However, this is considered to be of little significance because vitamin D facilitates calcium absorption to a much higher extent. Parathormone influences the conversion of hydroxylated vitamin D (25, hydroxychole calciferol) to dihydroxychole calciferol in kidney which is more potent in increasing intestinal absorption.
Functions of Parathormone:
The function of parathormone can be summarized as follows:
(a) It enables more calcium to remain in blood serum and mobilizes Ca and P from bones.
(b) It regulates the permeability of blood vessels probably through calcium metabolism.
(c) The hormone controls the balance of inorganic ions in blood through its influence on calcium metabolism. Hypoactivity of the gland leads to tetanus, leading to heightened neuromuscular irritability. Under normal conditions inorganic ions in blood remain in a balanced state. Ca and Mg are neurosedative while Na and K are neuro excitatory. In tetany, serun calcium level is low and the level of excitatory factors increases leading to neuro-muscular irritability.
(d) In hypoparathyroidism, the creatine phosphate in muscle diminshes. Thus, parathormone influences creatine metabolism.
Control of Parathyroid Secretion:
1. By Ca Content of Blood:
In the normal routine, the Ca content of the blood itself determines the parathormone secretion. The relation is reciprocal. Parathyroid controls blood Ca, while blood Ca controls parathyroid secretion.
2. Endocrine Control:
The parathyroid controls its secretion through parathyrotropic hormone of anterior pituitary. Sometimes, thyroid may also influence the parathyroid secretion as in hyperthyroidism mobilisation of Ca from bones takes place.
Essay # 5. Hormones Secreted by Pituitary Gland:
The pituitary, a small oval structure (10 × 6 × 13 mm in man), lying in the sella tunica of the sphenoid bone, is attached to the hypothalamus by a slender stalk. This gland is now known as hypophysis. On the basis of cell-type and embryology anatomically it consists of two parts, the adenohypophysis (anterior lobe) and neurohypophysis (posterior lobe).
Adenophysis consists of the large pars distalis (pars anterior), the pars tuberalis and the pars intermedia. The pars intermedia is separated from the pars anterior by the interglandular cleft. Neurohypophysis consists of neural lobe (pars nervosa) or infundibular process and infundibulum, which includes the stalk and median eminence (Fig. 5) outgrowths.
Hormones of Adenohypophysis:
Seven hormones have been demonstrated to originate from the adenohypophysis. Since at least five of these exert important regulatory actions on other endocrine glands, this gland is commonly known as a ‘a master of endocrine orchestra’,
The important hormones of anterior pituitary are as follows:
i. Growth Hormone or Somatotrophin:
Growth hormone is secreted by somatotrophs in the adenohypophysis. Human growth hormone is a linear polypeptide of 191 aminoacids and has a mol. wt. of about 21,500. Growth hormone composition differs from species to species.
In man growth hormone from other primates alone is effective while in non-primates the hormone from other species is equally effective. Growth hormone has a high turnover in plasma. It is broken down in liver and kidney. Plasma half-life is about thirty minutes.
ii. Action of Growth Hormone:
Growth hormone exerts profound effect on cellular metabolism and growth. The metabolism of protein, fat and carbohydrate is influenced by this hormone.
(a) Protein Metabolism:
Growth hormone stimulates the uptake of aminoacids even in the absence of protein synthesis. The incorporation of aminoacids into protein during protein synthesis is also increased by this hormone. The level of aminoacids in blood, and urea nitrogen excretion through urine are decreased. A positive nitrogen balance is promoted.
(b) Fat Metabolism:
Fat is mobilized from adipose tissue and breakdown of the stored fat is promoted by growth hormone. Consequently free fatty acids are released into circulation.
(c) Carbohydrate Metabolism:
The utilization and uptake of glucose by tissues is inhibited by growth hormone. Glucose output by liver is increased. All these lead to increase in blood glucose level.
Growth Hormone and Growth:
Growth hormone is necessary for the overall growth of the body after the birth of child. However, regeneration, wound healing, hair growth and pubertal changes are not regulated by this hormone.
Growth hormone controls growth of the bones, especially the formation of cartilage, in association with three peptides known as “somatomedins.” Somatomedin A (mol.wt. 7000) is concerned with the incorporation of sulfate into chondroitin sulfate in cartilage of epiphyses.
Somatomedin B controls cell replication (thymidine incorporation into DNA), and conversion of proline into collagen hydroxy proline. Somatomedin C promotes both of the above processes. Growth hormone promotes the formation of somatomedins by liver and kidney.
Normal growth pattern is disturbed by secretion of abnormal levels of growth hormone. Deficiency of growth hormone leads to dwarfism while excessive secretion produces gigantism and acromegaly.
Control of Growth Hormone Secretion:
A variety of chemical and neural factors control growth hormone secretion. All these factors involve the adrenergic system of the brain and depend upon the integrity of the hypothalamo-pituitary system.
Growth hormone secretion is stimulated by hypoglycemia, fasting and decrease in plasma free fatty acids, all of which can be grouped as decrease in energy substrate. Increase in plasma aminoacids level, stress, deep sleep and growth hormone releasing hormone are other factors which stimulate secretion.
Hypoglycemia:
Intracellular glucose deficiency stimulates growth hormone secretion. This response is particularly useful in protecting brain from glucose deficiency as growth hormone decreases glucose utilization in peripheral areas.
Fasting:
Growth hormone level increases during fasting but it is not the main metabolic regulator during fasting. The glucose conserving and fat mobilizing property of growth hormone is particularly benificial during fasting.
Decrease in Plasma Free Fatty Acids:
Growth hormone promotes mobilization of stored fat and increases the plasma level of free fatty acids. However, there is no conclusive evidence for increased secretion of growth hormone under conditions of low FFA level in plasma.
Increase in Plasma Amino Acids:
Growth hormone increases amino acids utilization by tissues and protein synthesis. Increase in the level of circulating amino acids stimulates secretion of growth hormone. Such stimulation can be observed by infusing of certain amino acids intravenously.
Stress:
Physical as well as mental stresses increase growth hormone secretion. Surgical stress, pain, strenuous exercise, bacterial endotoxins and emotional stress all stimulate growth hormone secretion. In all these cases the adrenergic system of the brain is involved.
Deep Sleep:
Deep sleep is accompanied by marked elevation in the level of growth hormone. The importance of this phenomenon is not understood.
Short Feed Back Control:
As there is no definite target site for growth hormone there can be no feed back control by target gland hormones. Growth hormone may influence its own secretion by exerting an inhibitory effect on the release of growth hormone releasing hormone (GHRH) produced by the hypothalamus.
This hormone is a small acidic peptide containing 11 amino acids. Administration of the extract of median eminence of hypothalamus leads to increased growth in young rats. GHRH levels in hypothalamus are reduced by starvation and increased by thyroxine. Growth hormone secretion is also under feed back control of somatomedins. High plasma levels of growth hormone are found in children unable to produce somatomedins (Laron dwarfs).
Melanocyte Stimulating Hormone (MSH):
It is polypeptide in nature and was formerly regarded as intermedin. It is found in two forms, α MSH and β MSH.
MSH effects pigment dispersion in the melanophores of lower vertebrates. However, its role in birds and mammals has been uncertain. It stimulates melanin synthesis in mammalian skin. It clearly stimulates production of new pigments especially in fishes and amphibians.
The secretion of MSH is depressed by glucocorticoids as the cases of adrenocortical insufficiency are subjected to melanization. (Addison’s disease).
In addition to the above hormones the adenohypophysis is also believed to secrete the following hormones:
1. Metabolic Hormone:
It stimulates the tissue cells to account for higher rate of metabolism.
2. Diabetogenic Hormone:
It is secreted by the acidophils and is antagonistic to insulin. It increases the blood sugar level.
3. Glycotropic Hormone:
It is supposed to be produced by basophil cells. It helps the action of adrenaline. Its action is to retard the withdrawal of glucose by the tissue cells from the blood stream, and thus it is antagonistic to insulin.
4. Ketogenic Hormone:
Secreted by acidophils and mobilises fats from the depots and accelerates the formation of ketone bodies in the liver.
5. Pancreotropic Hormone:
It is believed to control the growth and activity of the Islets of Langerhan’s of pancreas.
6. Parathyrotropic Hormone:
There is some evidence to suggest that adenohypophysis controls the activity of parathyroid glands by the production of a hormone, called parathyrotropic hormone.
Adenohypophysis and Other Endocrine Glands:
Anterior pituitary directly or indirectly controls other endocrine structures.
The relationship of adenohypophysis to other important endocrine glands is as follows:
a. Adenohypophysis and Gonads:
The relation between the two is reciprocal. The gonadotrophs of the adenohypophysis control the development and the activity of the sex glands. Whereas, the sex hormones inhibit the gonadotropin secretion from adenohypophysis. Similarly, prolactin stimulates the production of progesterone, while the latter and the estrin inhibit prolactin production.
b. Adenohypophysis and Thyroid:
Relation is reciprocal.
c. Adenohypophysis and Adrenal Cortex:
Adenohypophysis controls the activity of the adrenal cortex through its secretion ACTH. Adrenal cortex perhaps also influences the adenohypophysis.
The hormonal inter-relationship is shown in Fig. 6.
Neurohypophysis:
Anatomically the posterior lobe of pituitary or neurohypophysis includes the neural division and pars intermedia. The neural division is made up of pars nervosa, infundibulum and median eminence. In lower vertebrates the salk and the pars nervosa are hollow with a central canal, continuous with the third ventricle being the remnant of the original lumen of the nervous down growth. It is absent in man but present in cat.
The pars nervosa consists of ependymal cells, mossy neuroglial cells and pituicytes. The pituicytes are the chief cells which make bulk of gland. These cells are believed to secrete the hormones of neurohypophysis.
Two tracts of non-medullated nerve fibres arise from the hypothalamus and supply the posterior lobe. Tubero-hypophysial tract originates from the median eminence of tuber cinerium and passes along the posterior wall of the stalk and enters the gland.
Supraoptic-hypophysial tract arises from the supraoptic paraventricular nuclei passes down along the anterior wall of the stalk and enters the neural lobe ending round the blood vessels and the gland cells. These tracts contain only motor fibres. The growth and activity of neurohypophysis depends on the stream of motor impulses from the hypothalamus and reaching the gland through these tracts.
The hormones of neurohypophysis are now clearly established to be formed in the supraoptic and paraventricular (tuber cinerials) nuclei of the hypothalamus and later transported within nerve fibres to the neurohypophysis, there to be liberated in blood stream upon appropriate stimulus.
Hormones of Neurohypophysis:
The neurohypophysis secretes two hormones, the antidiuretic hormone (arginine vasopressin) and oxytocin. These hormones are synthesized in two hypothalamic nuclear areas and pass to the neurohypophysis through nerve axons. This process in known as neurosecretion. The hormones are stored in posterior pituitary and are released into the blood.
Chemistry and Metabolism of Hormones:
Arginine vasopressin and oxytocin are protein hormones. They are octa peptides and have closely related structures. Although structurally similar, the two hormones have different specific functions. Oxytocin has less than 1% of the antidiuretic action of vasopressin, and the latter has only 10 to 20% of effectiveness of oxytocin on mammary glands and uterus.
Vasopressin is an octapeptide having a molecular weight of about 1100. Oxytocin is also a peptide with eight aminoacid residues and has a molecular weight of 1000. Vasopressin is synthesized by the supra optic nucleus and oxytocin by the paraventricular nucleus.
The two hormones are synthesized from component amino acids within the cytoplasm of the cell bodies of the neurones. Secretory granules containing the two hormones, probably bound to protein are released from the cell bodies pass down the axons to the posterior pituitary and this process consumes about ten hours.
At the nerve ending within the posterior lobe the two hormones are bound to small proteins (Mol. Wt. 10000) known as neurophysins. The binding to protein helps in storage as well as release mechanism. On receiving appropriate stimulus through the axons from the two nuclear areas, the hormones are released from the nerve endings through exocytos is vasopressin.
Action on Kidney:
The principal target site of vasopressin in mammals is kidney. The hormone acts on distal convoluted and collecting tubules and increases their permeability to water. Cyclic AMP is involved in the process and the increase in permeability may be due to increase in the number of hypothetical pores or in their size. Increase in the activity of the enzyme hyaluronidase can increase the permeability of the intercellular ground substance.
Vasopressin can influence blood flow in the kidney by increasing flow in the cortex and reducing the flow in medulla. This helps in water reabsorption by reducing blood flow in vasa recta, thus the counter current multiplier system becomes more effective. The hormone reduces chloride absorption and thus increases chloride loss.
Action on Heart and Blood Vessels:
Vasopressin is a potent pressor agent. However, at normal physiological plasma concentration, the pressor effect is not significant. Under haemorhagic conditions, the plasma vasopressin concentration increases to such a level as to produce pressor effects. The hormone also raises blood pressure. The heart rate is reduced reflexly due to high blood pressure.
Action on Smooth Muscles:
The contraction of the smooth muscles in the walls of urinary bladder, and uretor are increased. The contractions of stomach and intestine are increased.
Control of Secretion:
The secretion of vasopressin is regulated by a number of factors as shown in Fig. 7.
(1) Vasopressin secretion is stimulated under conditions of severe dehydration and water deprivation.
(2) Dilution of blood due to excessive drinking of water leads to fall in the osmotic pressure. Such a condition acts on the hypothalamus and secretion of vasopressin is reduced. Consequently, water reabsorption by kidney is reduced and large volume of urine is excreted.
(3) Increase in the colloid osmotic pressure of the blood due to water deprivation or increase in chloride content, urea or glucose concentration promotes secretion of vasopressin.
(4) Haemorhages resulting in decrease in blood volume release vasopressin. This response is not observed if vagus nerve is cut, as affarent pathway from low pressure receptors in the left auricle is interrupted.
Oxytocin:
Action on Mammary Gland:
Oxytocin is very important for the mechanism of ejection of milk from the mammary gland through nipple. Milk present in sinuses, cisterns and large ducts can be removed passively but milk in the secretory alveoli and smaller ducts can be expelled only actively. Oxytocin is responsible for the contraction of myoepithelial cells around the alveoli and along the small ducts of the glands resulting in expulsion of milk.
Action on Uterus:
Oxytocin plays an important role in facilitating the expulsion of embryo from uterus once labour has set in. However, the hormone does not initiate parturition, and its effect on the uterus of a virgin is negligible.
Uterine myometrium is composed of smooth muscles which can show rhythmic contractions on depolarization. Oestrogen increases this activity while progesterone suppresses it. At the end of pregnancy sensitivity to oxytocin increases.
During labour, cervix is stretched and this stimulates secretion of oxytocin. From this point onwards, oxytocin is the principal stimulus that promotes rapid movement of the fetus through birth canal. Oxytocin increases the sensitivity and contractile activity of the smooth muscle cells potentiated by oestrogen.
Sperm Transport:
Recent evidence indicates that coitus stimulates oxytocin release. Oxytocin acts on the uterine smooth muscles and the resulting uterine contractions aid the transport of spermatozoa into the fallopian tubes.
Control of Secretion:
Milk Ejection Reflex:
The act of suckling stimulates the tactile receptors, thermoreceptors and pressure receptors in the nipple and promotes the secretion of oxytocin by a neuroendocrine reflex (Fig. 8). The impulses are conducted by affarent nerves to the spinal cord and through ascending tracts to the paraventricular and supraoptic nuclei where they form synapses. The stimuli initiate neurosecretion of the hormone into circulation.
A latent period of about one minute exists between suckling and milk secretion.
Stimulation of Female Genital Tract:
The act of coitus can cause oxytocin release resulting in increased uterine wall contractions which help in passage of sperms increasing the chances of fertilization. The stimuli generated from coitus via neuroendocrine reflex, similar to milk ejection reflex, can increase oxytocin secretion.
During parturition, the fetus engages with the cervix and stimulates the sensitive mechanoreceptors. A neuroendocrine reflex thus initiated releases oxytocin. Oxytocin inturn stimulates the uterine myometrial contractions ensuring the expulsion of the fetus as soon as possible.
The release of oxytocin during labour not only helps in parturition but also promotes milk ejection ensuring that the new born gets milk during its first suckling. In animals where more than one young one is born, the suckling of milk from mammary gland by the first born stimulates the production of more oxytocin which aids in the birth of the subsequent.
Factors Influencing Oxytocin Release:
Normal reflexes from mammary glands to hypothalamus can be inhibited by a variety of somatic and mental stresses. Pain or discomfort, breast feeding under embarassing conditions, anger, fear and mental tension decrease the secretion of oxytocin.
Essay # 6. Hormones Secreted by Adrenal Glands:
The paired adrenals are located on the dorsal side of the kidneys as yellowish-brown glands, one on each kidney (hence, the name adrenal or suprarenal). Each adrenal is enclosed in a capsule and consists of an outer part —the cortex and an inner part, the medulla. The cortex is yellowish and medulla is brownish in colour. The two parts are structurally, functionally and embryologically distinct.
Cortex is derived from the mesodermal coelomic epithelium of the anterior part of the mesonephros, while medulla is ectodermal in origin and is derived from the tissues from which the sympathetic ganglia develop. The primitive medullary tissue at first lies outside which later on migrates laterally to be invested by the cortical tissue.
Hormones of Adrenal Cortex:
Crude extract of the adrenal cortex is known as cortin, which contains three groups of active principles, two of which being the steroids and the third one of unknown composition.
The zona glomerulosa secretes the mineralocorticoid aldosterone while the second layer Zona fasciculata produces the glucocorticoids, Cortisol and corticosterone. The inner layer. Zona reticularis synthesizes sex steroids, both androgens and oestrogens.
Chemistry and Metabolism of Hormones:
Structure:
All the hormones secreted by adrenal cortex are steroids with a cyclopentanoperhydro phenanthrane nucleus and are derived from cholesterol (Fig. 9). There are four rings to which are attached the functional groups, -H, -CH3 – – – OH, = O either above (α) or below (β) the ring.
The steroid hormones can be differentiated into two main types:
(i) With a two carbon side chain attached to the 17th Carbon atom in ring known as 21 carbon steroids, and
(ii) With either an = O or -OH group attached to carbon 17 called as C19 steroids.
The C19 steroids are androgenic but removal of one more carbon atom results in C18 compounds with oestrogenic properties. The C21 steroids show both mineralocorticoid and glucocorticoid properties. For normal adrenocorticoid activity, a double bond between C4 and C5 and a ketone group at C3 are necessary.
For glucocorticoid activity an = O or —OH group at C11 is essential. The presence of a —OH group at C17 further enhances the glucocorticoid activity. For mineralocorticoid activity the presence of an = O or —OH group at C 21 is very essential.
Glucocorticoids:
These are C21 steroids with = O or – OH at C11 position.
(1) 11 Dehydrocorticosterone possesses an = O at 11C position and has moderate sodium and carbohydrate activity.
(2) Corticosterone differs from dehydrocorticosterone in having a —OH group at 11C position. It also shows moderate sodium and carohydrate activity.
(3) Cortisone possesses a = O group at 11C position and a —OH group at 17C. It is 17 hydroxy-11 dehydrocorticosterone with weak sodium and strong carbohydrate activity. It also has potent anti-inflammatory activity.
(4) Hydrocortisone or Cortisol is 17-hydroxy corticosterone with a —OH at 11C position. This compound also shows strong carbohydrate and powerful anti-inflammatory activity.
Mineralocorticoids:
These are steroid hormones with a —OH or = O at 11C position and a = O or —OH at 21C position.
(1) Aldosterone occurs in both hemiacetal – and aldehyde forms. The characteristic feature of this hormone is a methyl group at C18 position is replaced by an aldehyde group. It shows very strong sodium retention activity and mild carbohydrate activity.
(2) Deoxycorticosterone is without a = O or —OH group at 11C position. It also shows powerful sodium retention and mild carbohydrate activity.
(3) 17-hydroxy 11-deoxycorticosterone is with a-OH group at 17C and without a-OH or = O at 11C position. It has mild sodium retention activity.
Sex Steroids:
These are C19 compounds with a = O or —OH or a side chain CO-CH3. Examples are androsterone, dehydroepiandrosterone, oestradiol, and progesterone.
Biosynthesis:
The synthesis of adrenocorticoids takes place in the endoplasmic reticulum and mitochondria. The parent substance cholesterol is partly taken up from the blood and partly synthesized in the endoplasmic reticulum from acetate and acetyl coenzyme A. Cholesterol is stored in the form of a cholesterol ester and is released whenever required by the action of lipase.
This release is a rate limiting step in the biosynthesis of glucocorticoids and is controlled by ACTH. Free cholesterol is converted to Δ5 pregnenolone by pregnenolone synthetase in the mitochondria. Pregnenolone acts as a pivot for the synthesis of all the adrenocorticosteroids (Fig. 10).
In the smooth endoplasmic reticulum, pregnenolone is converted to progesterone which is hydroxylated at C21 of C17. Further hydroxylation of the C21 compound at C11 in the mitochondria yields corticosterone. Similarly hydroxylation of the C17 derivative in the smooth endoplasmic reticulum leads to the formation of Cortisol.
In Zona glomerulosa, corticosterone undergoes hydroxylation and dehydrogenation at the C18 position to form aldosterone. In Zona reticularis, pregnenolone is converted to 17-α-hydroxypregnenolone and the side chain at C17 position is detatched to yield the C19 compound dehydroepiandrosterone which finally undergoes dehydrogenation producing androstenedione. The synthesis and release of adrenocortical hormones is controlled by ACTH.
Transport, Metabolism and Excretion:
Adrenocorticsteroid hormones are circulated mostly in bound form and only a small quantity is free. Glucocorticoids and mineralocorticoids bind with plasma proteins. An α-globulin, corticosteroid binding globulin or transcortin binds with Cortisol and corticosterone. A β-globulin sex hormone binding globulin or gonadal steroid binding globulin transports oestradiol and testosterone.
Adrenal cortical hormones are metabolized in liver kidney and gut. Cortisol is converted in liver to cortisone. Both Cortisol and cortisone are reduced in the liver to dihydrocortisol and dihydrocortisone respectively and loose the double bond between C4 and C5. These compounds are hydroxylated at C3 to tetrahydrocortisone and tetrahydrocortisol which are converted to glucuronides by conjugation at the C3 hydroxyl group.
The process occurs mostly in liver and to a minor part in kidneys. As the glucuronides are water soluble, they are excreted through urine. Some part of tetrahydrocortisol and tetrahydrocortisone are converted to cortol and cortolone. These two compounds are oxidised to 17 ketosteroids which have weak androgenic action; they are excreted in urine in conjugated form as sulfates (Fig. 11).
Aldosterone weakly bound to plasma protein is separated in liver and converted to tetrahydro aldosterone glucuronide which is excreted through urine.
Action of Glucocorticoids:
Glucocorticoids act on various tissues and perform many functions. They play an important role in carbohydrate, lipid, protein and purine metabolism and have influence on cardiovascular, skeletal muscle, central nervous system, lymphoid, connective and other tissues. They exert strong anti-inflammatory effect and help to cope up with stress (Fig. 12).
Carbohydrate Metabolism:
Glucocorticoids play an important role in the maintenance of glycogen reserves in liver, heart and skeletal muscle.
Glycogen production is stimulated by promoting gluconeogenesis. Protein breakdown is enchanced thereby releasing free aminoacids. For this purpose, they induce synthesis of specific proteins, such as transaminases which catalyse the transfer of α-amino groups to α-ketoglutarate, thus providing a path way for their conversion to carbohydrate.
Glucocorticoids show an anti-insulin effect in peripheral tissues by inhibiting uptake of glucose. Similar effect is also seen in skeletal muscle.
Protein Metabolism:
Protein breakdown in peripheral tissues is increased by excessive glucocorticoid secretion, leading to negative nitrogen balance. Their deficiency results in retarded growth due to loss of appetite and reduction in aminoacid absorption by the intestine.
Lipid Metabolism:
Glucocorticoids inhibit lipid synthesis in peripheral tissues by inhibiting glucose uptake. This results in reduced formation of glycerophosphate that is required for re-esterification of fattyacids. Glucocorticoids increase the level of free fatty acids and potentiate the lipolytic response to agents such as growth hormone and catecholamines.
Circulatory System:
Normal circulation is dependent upon glucocorticoids and adrenalectomy results in circulatory collapse due to impaired myocardial function and fall in peripheral resistance.
Skeletal Muscle:
Glucocorticoids are essential for normal muscular activity. Deficiency of these hormones causes rapid muscle fatigue and excess leads to muscular atrophy due to protein breakdown and circulatory failure. Another possibility is release of lysosomal enzymes due to increased fragility of lysosomes in the absence of glucocorticoids during muscular activity.
Nervous System:
Brain is very sensitive to glucocorticoids level. Variation in the level of the hormones leads to detectable changes in the threshold to sensations such as memory, concentration and intelligence. Deficiency of glucocorticoids decreases cerebral activity, producing apathy and lassitude. Excess hormones produce euphoria, insomnia and hyperactivity.
Lymphoid and Connective Tissue:
Deficiency of glucocorticoids leads to hyperplasia of lymphoid tissue and increase in the number of circulating lymphocytes. Administration of glucocorticoids dissolves the lymphoid tissue, and decreases the lymphocyte number. Lymphocyte nuclei become pyknotic and cytoplasm is lost. Cells are finally phagocytosed.
Glucocorticoids inhibit fibrosis and other collagen diseases. Mucopolysaccharide synthesis is inhibited; hyaluronic acid polymerization is increased. The ground tissue composition is altered.
Anti-Inflammatory Action:
The number of mast cells which produce histamine at the site of injury leading to inflammation is reduced by glucocorticoids. The response of cells to inflammation is modified by glucocorticoids. The number of polymorphonuclear lymphocytes is increased.
The phagocytic activity stickiness and digestive capacity of lymphocytes and monocytes is reduced. Antibody formation in response to primary antigenic stimuli is reduced by inhibiting division of plasma cells. The number of eosinophils is also reduced.
Water Metabolism:
Glomerular Alteration rate is controlled by glucocorticoids. Deficiency of these hormones increases water retention leading to water toxicity.
Mineralocorticoids:
The principal mineralocorticoid secreted by adernal cortex is aldosterone which promotes the reabsorption of sodium from body fluids such as sweat, urine, saliva and the contents of gastrointestinal tract (Fig. 13). Na+/K+ exchange across cell membrane of different tissues is also increased.
In kidney, aldosterone acts on the distal convoluted tubule and increases the absorption of sodium in exchange for potassium or hydrogen ions. The same process occurs in proximal convoluted tubules also. Continuous administration of aldosterone results in loss of potassium from the intracellular fluid and partial replacement by sodium.
With increase in the concentration of plasma sodium level, water is also retained and the extracellular fluid volume increases. However, oedema does not occur because glomerular filteration rate is increased. The mechanism of action of this hormone is thought to promote the synthesis of an enzyme protein that regulates the rate of oxidative phosphorylation and release of energy for active transport (Fig. 13).
Hormonal Control:
Adrenocorticotrophic hormone (ACTH) is the only known factor. Intravenous administration of ACTH C 0.5 ng/kg body weight increases glucocorticoid production within two to three minutes. ACTH secretion is regulated by corticotrophin releasing factor from hypothalamus (Fig. 14).
Feed back control. Increase in the concentration of glucocoroticoids in blood depresses, while decrease in their level increases ACTH secretion by anterior pituitary gland. This process is known as “feed back” mechanism. In the hypothalamus, corticotrophin releasing factor secretion is influenced by negative feedback control from the Cortisol level of blood. A direct feedback control of the corticotrophin producing cells in the pituitary by Cortisol is also present (Fig. 14).
Nervous Control:
The corticotrophin releasing factor releasing neurons are excited directly by acetylcholine releasing neurons and indirectly by neurons releasing 5-Hydroxytryptamine. Stress, cold and excitement like factors stimulate hypothalamus which releases a chemical mediater, the corticotrophin releasing factor. That is carried by local blood circulation to corticotroph cells in the adenohypophysis. ACTH secreted by these cells is carried by blood to adrenal cortex which in turn secretes corticosteroids.
Mineralocorticoids Control:
Aldosterone secretion is influenced by ACTH, high plasma K+, low plasma Na+ and ACTH. These factors promote conversion of cholesterol to pregnenolone.
The importance of ACTH in mineralocorticoid control is species dependent. ACTH can influence aldosterone secretion indirectly by promoting the release of Cortisol and corticosterone which although possess very little mineralocorticoid activity, can exert salt retaining effect if present in large quantities. Increase in plasma potassium concentration increases aldosterone secretion, while steep fall in plasma sodium level increases aldosterone secretion.
Renin-Angiotensin System:
The liver releases an α-2 globulin angiotensinogen or renin substrate peptide into the blood. Renin is a proteolytic enzyme (mol. wt. 42000) secreted by the juxtaglomerular cells in the kidney. The juxtaglomerular cells are sensitive to changes in the diameter of renal arteriole and renin converts angiotensinogen into a decapeptide angiotensin I.
This inturn looses two more aminoacids due to the action of a converting enzyme to form an octapeptide, angiotensin II. This substance stimulates increased synthesis and release of aldosterone from the zona glomerulosa cells. Angiotensin II is quickly inactivated by peptidases in plasma.
The adrenal medulla consists of polyhedral cells. These are postganglionic sympathetic cells without axons. The secretions are directly released into the blood. The medullary cells form a series of irregular columns around venous sinusoids. Each cell contains dense cored vesicles called chromaffin granules containing catecholamines. The cells depending upon the type of vesicles can be divided into adrenaline storing and noradrenaline storing cells.
Chemistry and Metabolism of Catecholamines:
All the three catecholamines are derived from the aminoacid phenylalanine. In liver this aminoacid is hydroxylated to form another aminoacid tyrosine. Tyrosine reaches through blood circulation the adrenal medulla. In the adrenal medullary cells, tyrosine hydroxylase converts it to dihydroxypltenylalanine and then to dopamine by the action of aromatic-L-aminoacid decarboxylase.
From the cytoplasm of the adrenal medullary cells, dopamine enters the dense core vesicles in which it is converted to noradrenaline by dopamine β-hydroxylase. In the adrenaline storing medullary cells, noradrenaline passes into the cytoplasm and undergoes methylation catalyzed by the enzyme phenylethanolamine -N-methyl transferase to form adrenaline. Adrenaline again reaches the vesicles and is stored in them until released (Fig. 15).
Adrenaline and noradrenaline undergo rapid degradation after their release. The two hormones are either physically removed from circulation by uptake into noradrenergic nerve endings or other tissues, or they are metabolised within blood or tissues by an enzyme, catechol -o-methyltransferase. The products formed are metadrenaline and non-netaadrenalinc which may be either excreted in urine or oxidised ultimately to vanillylmandelic acid and excreted in urine (Fig. 16).
Action of Adrenaline and Noradrenaline:
Adrenaline and noradrenaline are known as “emergency” hormones released under conditions of ‘”fright, fight or flight”. The release of the hormones is invariably associated with the activity of sympathetic nervous system.
Adrenergic Receptors:
Within the cells the hormone binds to specific receptors located on or inside the cells, the adrenergic receptors.
These receptors are of two types:
i. α and
ii. β.
i. α-receptors:
They respond to noradrenaline and α-actions involve contraction of smooth muscles.
ii. β receptors:
They respond to adrenaline and involve relaxation of smooth muscles or metabolic effects, α-actions are due to inhibition of adenyl cyclase while β actions involve activation of this enzyme, α-receptors are excitatory whereas β receptors are inhibitory.
Heart and Blood Vascular System:
Both adrenaline and noradrenaline increase heart rate by stimulating the sinuauricular node. Myocardial contractility, and excitability are increased as a result of which the force of contraction is increased. Conduction through the bundle of his is also increased. All these effects are β effects and help to increase the cardiac output.
Vasodilation of the coronary blood vessels and vasoconstriction of the peripheral vessels also occur due to action by noradrenaline. Adrenaline mediates β vasodilation of the skeletal blood vessels. Blood pressure increases sharply and comes to normal or below normal level slowly.
Respiration:
Bronchioles are dilated. Mucus secretion is reduced and mucosa undergoes shrinkage. The respiratory rate and depth are increased.
Skeletal Muscles:
Muscular excitability and contractility are increased, and onset of fatigue is delayed.
Metabolism:
Adrenaline and noradrenaline promote glycogenolysis in liver and muscle, and lipolysis. Oxygen consumption by tissues and heat production are increased. All these are β effects. Blood glucose level rises due to glycogenolysis and gluconeogenesis due to increased liberation of glucocorticoids as a result of increased production of ACTH.
Other Effects:
(i) Sweat glands are stimulated and sweating is increased,
(ii) During excitement, smooth muscles of the skin contract. Contraction of the erector pili muscles causes standing of the hairs of mammals, spines of porcupine and feathers of birds,
(iii) Intestinal movements are inhibited and sphincters are closed. Gall bladder is contracted,
(iv) Urinary bladder is relaxed, urinany volume is reduced due to reduction in renal circulation,
(v) Salivary secretion is increased,
(vi) Adrenaline produces restlessness, anxiety and fatigue.
Sympathetic Discharge:
The combined action of the discharge of sympathetic nerves, and adrenaline and noradrenaline by adrenal medulla, produce an emergency response in animals to prepare then for fight or flight. Blood pressure and cardiac out put increase and blood is diverted to skeletal muscle and glycogenolysis and lipolysis provide fuel for muscle metabolism.
Increased respiratory rate and bronchodilation stimulate respiratory exchange of gases. Spleen contracts and releases erythrocyte rich blood into circulation, Piloerection gives an aggressive appearance.
Control of Adrenomedullary Secretion:
Adrenal medulla produces no hormones in resting condition. A variety of ‘stressful’ conditions stimulate the secretion. These are hypoglycemia, hypoxia, asphyxia, acidemia, hypothermia, heamorrhage, hypotension and exercise. Emotional disturbances such as anger, fear, pain, sexual excitement, also stimulate the adrenal medulla. These conditions stimulate the splanchnic nerves that innervate the adrenal gland.
Essay # 7. Hormones Secreted by Reproductive Glands:
The paired testis are abdominal in all the vertebrates except the higher mammals wherein they are extra-abdominal, being enclosed in the scrotal sac. Each testis consists of a large number of seminiferous tubules and many isolated groups of interstitial cells, which secrete the male hormone and pour it into the blood stream. Thus, testes are both exocrine as well as endocrine in function.
Active Principle (Hormone) of Interstitial Cells of Testis:
The interstitial cells of testis, which represent the endocrine tissues of testis, secrete a hormone, the testosterone.
The removal of both the testes before puberty results in the subject sterile and childish. After puberty the subject becomes sterile and generally the secondary sexual characters are degenerated on removal of both the male sex glands. However, the ill-effects of the removal of the testes may be rectified by injecting the testicular extract.
These experiments show that in addition to spermatogenesis the testes elaborates a hormone, on which the growth of secondary sex organs and secondary sexual characters depend. This hormone is known as testosterone.
Thus in the words of Moore:
“The testicle exercises two principal functions; it produces spermatozoa, which are necessary for fertilization, and it secretes a substance or substances (hormone) that play an important role in the organism. This hormone regulates the function of numerous special accessory reproductive organs epididymis, vas deferens, prostates, seminal vesicles etc., that make possible the delivery of spermatozoa to the place where fertilization can occur, and at least in sub-primate vertebrates the hormone initiates the sexual drive or inclinations to mate with females. The sex urge in man is not so clearly or exclusively dependent upon the hormone action since imitation, custom and psychology play such a great role in human conduct.”
Testosterone is an androgen which is also produced by adrenal cortex. Androgens are substances having masculinising properties. Their administration causes growth of accessory sex organs in the castrated male, and growth of comb, wattles and the car lobules of the castrated male birds.
Testosterone (natural androgen) is destroyed by the liver, hence orally it is not effective while the synthetic androgens (methyltestosterone and testosterone propionate etc.) are not effected by liver. They are sterols.
Functions of Testosterone:
(1) Growth of accessory sex organs.
(2) Development of male secondary sex characters.
(3) Increases the span of life and fertilizing power of the spermatozoa.
(4) Inhibits thymus —at puberty the thymus is involuted.
Control of Secretion:
The secretion of testosterone by the interstitial cells (cells of Leydig) is predominantly regulated by the leutinizing hormone of anterior pituitary.
Fate of Testosterone:
It is believed that androsterone and dehydroandrosterone excreted with the urine are the derivatives of testosterone, which during its metabolic processes, becomes changed into these forms and are excreted with urine.
The paired ovaries lie in the abdominal cavity, one on either side hanging from the broad ligament by a fold of peritoneum called the mesovarium. Ovaries show much histological variations at different phases of life. It is most active at puberty and breeding period. However, the different development stages of the ova may be seen at all the phases of life.
Fundamentally ovary consists of a layer of germinal epithelium, stroma consisting of connective tissue, in which the developing follicles way be seen and the groups of interstitial cells.
The latter form the endocrine part of the ovaries, which secrete a hormone estrogen. Besides this the corpus luteum developed from the ruptured follicles after ovulation also produce a hormone progesterone. Thus, ovary is known to produce two hormones, namely the estrogen and progesterone.
Estrogen:
Estrogens are in general the compounds which can produce oestrus in ovariectomised animals, and are of two varieties, the synthetic and natural. Natural estrogen is secreted by the interstitial cells of the ovary and is known as estradiol. Other estrogens like esterone and estriol are found in the adult female urine and are believed to be the derivatives of estradiol, which are excreted as glucuronates. Estrogens are also produced by the adrenal cortex and placenta.
Functions of Estrogens:
(1) Responsible for all the puberty changes. They bring about the growth of uterus, vagina, development of breasts, menstrual changes and the appearance of secondary sexual characters.
(2) They are also responsible for the growth of uterus during pregnancy.
(3) They increase the sensitiveness of the uterine muscles to the action of oxytocin and is antagonistic to the action of progesterone which depresses it. At the full term pregnancy, progesterone level falls due to the degeneration of corpus luteum while that of estrogens still remains high and thus they enhance oxytocin effect and thus parturition starts. Thus, estrogens exert synergistic action with oxytocin.
(4) Administration of estrogens causes water retention and increase.’ blood volume, while subjects of ovariectomy face water loss. Hence it may help water balance.
(5) The injection of estrogens in the adult male rats in large doses causes degeneration of male reproductive organs. Thus, they are antagonistic to androgens.
Fate of Estradiol:
The estradiol becomes changed into estrone and estriol after their action which are then combined with glucuronic acid in liver and are excreted with urine as glucuronates. The excretion of these estrogens is variable at different phases of life. It becomes maximum at the time of ovulation in mammals and just before the onset of parturition of placenta in the full term pregnancy.
Progesterone:
It is the active principle of corpus luteum. It is also produced by placenta and in traces by adrenal cortex. Corpus luteum is formed by the ruptured Graffian follicles after ovulation, which continue to produce its hormone till menstruation or till 4-5 months after the pregnancy has occurred. It is a sterol.
Functions:
(1) Progesterone is responsible for the premenstrual changes in uterine mucosa.
(2) Taken as essential in pregnancy.
(3) Enhances breast development during pregnancy.
(4) Inhibits ovulation.
(5) In mammals it also causes the enlargement of birth canal by the growth of vagina and relaxation of pelvic ligament.
During the metabolic processes progesterone gets reduced into an inactive derivative known as pregnanediol. It becomes conjugated with glucuronic acid and sodium in the liver and appears in the urine as sodium-pregnanediol glucuronate. It appears in the urine in the leuteal phase of menstruation but not in follicular phase.
The maximum excretion of progesterone with urine is about a week before the menstruation and ceases before the period starts. During pregnancy maximum secretion is during eighth or ninth month as it is produced by the placenta in large amount and the concentration falls before the parturition or delivery.
The fertilized ovum enters the uterus and gets its way into the hypertrophied endometrium and the ovum becomes embedded in the walls of uterus. That portion of mucous membrane, which intervenes between the ovum and the muscular layer of the uterus undergoes extensive proliferation and forms the so-called placenta.
Thus, placenta is a physiological connection between the developing embryo and the maternal tissue. It develops because of two stimuli, one from the progesterone of the corpus luteum and the other exerted from the developing embryo. Originally placenta consists of both maternal and foetal tissues.
Endocrine Function of Placenta:
In addition to serving the function of nutrition, respiration and excretion of the developing embryo, placenta serves to produce the following hormones, which are very essential for the embryonic development.
1. Estrogens:
Placenta secretes estrogens and perhaps it is the only source for their secretion at the late pregnancy phase. This is evident by the fact that the excretion of estrogens continues even after removal of both the ovaries during pregnancy.
2. Progesterone:
The secretion of progesterone from the placenta is evident by the fact that the excretion of its secretion continues even after bilateral ovariectomy.
3. Chorionic Gonadotropin:
Besides the above two, placenta is also supposed to produce a third hormone which is known as the chorionic-gonadotropin, which has the same effect as the leutenizing hormone of anterior pituitary or in other words it possesses the leutinizing and leuteotropic activities and its function is to maintain the corpus luteum until the placenta is capable of producing estrogens and progesterone which are necessary for the maintenance of placenta.
Essay # 8. Hormones Secreted by Thymus:
Thymus is partly endocrine and partly lymphoid gland and is situated below the thyroid. It gradually enlarges until puberty and then atrophies.
Histologically the thymus consists of a number of lobules, each of which consists of outer cortex and inner medulla.
Functions:
(1) It controls the growth of the skeleton as the extirpation of the gland in the young results in ill-developed skeleton.
(2) It helps in the development of sex glands but the latter inhibit the former. It is evident by the fact that thymus is atrophied and involuted after puberty.
Control of Secretion:
Thymus activity is accelerated by anterior pituitary and thyroid, while gonads and adrenal cortex are known to inhibit its activity.
Essay # 9. Hormones Secreted by Pineal Body:
A small cone-shaped, pineal gland is situated beneath the corpus callosum between the two superior colliculi. It originates as a diverticulum from the roof of the third ventricle. The cavity of the diverticulum later on gets obliterated.
Histologically it consists of parenchyma cells, which are large with eosinophil cells and neuroglia cells.
In human, it atrophies at the age of seven years and is filled up with calcium and magnesium phosphates and carbonates. Its function is still unknown and represents possibly dying gland.
Essay # 10. Gastrointestinal Hormones:
The mucosal lining of stomach and intestine is the largest and most diverse endocrine gland of the body. There are a number of endocrine cells which are not grouped into compact endocrine tissue but are scattered over the mucosal cells. These cells secrete specific chemicals which act upon adjacent cells by diffusion and not through circulation.
Some of the gastrointestinal hormones are also secreted by other areas. These hormones control the motility and secretory activity of the digestive system and are produced in response to specific chemical substances in the gut contents. Most of them are polypeptides (Fig. 17).
Gastrin:
Gastrin occurs in two forms:
(1) Gastrin 17 secreted by pyloric antrum and
(2) Gastrin 34 produced by upper small intestine.
Gastrin 17 contains seventeen aminoacids while Gastrin 34 contains in addition to the seventeen aminoacids at C-terminal end of Gastrin 17 another seventeen aminoacids, thus making a total of 34. Its half life is six times more than Gastrin 17, but its action is six times less effective.
From the pyloric antrum, two gastrins have been isolated, Gastrin I without sulfate and Gastrin II with ethereal sulfate. The two gastrins contain seventeen aminoacids and are equally active. The biological activity of gastrin lies in the first five aminoacids and a synthetic product with all the physiological functions of gastrin, Pentagastrin is synthesized and is used clinically.
Gastrin release is stimulated by moderate distention of pyloric antrum, vagal stimulation, meat extracts, aminoacids and 10% ethyl alcohol. Gastrin secretion is inhibited by acid and over distention of antrum.
Gastrins are:
(1) Increase gastric motility,
(2) Stimulate gastric gland cells to produce acid and pepsinogen,
(3) Pancreatic juice secretion, and
(4) Secretion of secretin by duodenal mucosa.
Pancreozymin-cholecystokinin:
Pancreozymin-cholecystokinin is secreted by the mucosa of duodenum when food material containing acid, lipids, peptones and fatty acids comes in contact with the duodenal mucosa. It is a poly-peptide containing 33 aminoacids, of which the five aminoacids from the C-terminal end are common with gastrin. Therefore, the actions of cholecystokinin and gastrin are common. This hormone stimulates the secretion of enzyme component of pancereatic juice and causes contraction of the gall bladder.
Secretin:
Secretin is also a polypeptide hormone containing 27 aminoacids produced by duodenal mucosa and upper jejunum when acid chyme enters these parts. Its structure is different from that of gastrin and pancreozymin-cholecystokinin, but shows similarities to glucagon. Secretin stimulates the secretion and release of the liquid non enzyme component of pancreatic juice, and inhibits gastric secretion.
Enteroglucagon:
Enteroglucagon is secreted by the wall of small intestine and colon in response to glucose intake. Its structure and functions are identical to pancreatic glucagon. It stimulates the β-cells of pancreas to produce insulin. The physiological actions of gastro intestinal hormones are shown in Fig. 17.
Caerulin:
Caerulin is a decapeptide produced by the skin of the frog Hyla caerulea. Its structure and functions resemble both gastrin and cholecystokinin-pancreozymin. It has strong stimulatory effect on the contractions of gall bladder.
Gastrone:
Gastric mucosa has a substance known as gastrone. It inhibits the secretion of gastric acid stimulated by histamine and gastrin.
Villikinin:
This hormone is secreted by the upper ileum stimulated by the entry of acid chyme. This hormone stimulates the movement of intestinal villi.
A summary of the sources, site of action and effects produced is given in the following table:
