The following points highlight the three physiological roles of adrenal hormones. The roles are: 1. Glucocorticoids 2. Mineralocorticoids 3. Adrenal Androgens.
Role # 1. Glucocorticoids:
Although glucocorticoids were originally so called because of their influence on glucose metabolism, they are currently defined as steroids that exert their effects by binding to specific cytosolic receptors.
(1) Effects on carbohydrate metabolism:
Cortisol is a hyperglycemic hormone that increases glucose as well as decreases utilisation of glucose by cells.
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It increases hepatic gluconeogenesis by:
(i) Stimulating gluconeogenesis enzymes,
(ii) Permissive effect in that they increase hepatic responsiveness to the gluconeogenesis hormones (glucagon, catecholamine) and
(iii) Increasing the release of substrates from peripheral tissues particularly muscles.
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The steroid also increases glycerol and free fatty acid release by lipolysis and increases muscle lactate release. Cortisol also enhances hepatic glycogen synthesis and storage by stimulating glycogen synthetase activity and to a lesser extent by inhibiting glycogen breakdown.
However, these effects are insulin-dependent. Glucocorticoids decrease glucose uptake and utilisation in muscles, adipocytes and lymphoid cells by inhibiting membrane transport of glucose into those cells.
(2) Effects on protein metabolism:
Cortisol reduces the utilisation of amino acids for the formation of protein, everywhere except in the liver.
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It increases protein catabolism in extra-hepatic tissues like muscles, lymphoid cells, adipocytes by:
(i) Decreasing amino acid incorporation into tissue proteins and
(ii) Activating enzymes required for amino acid catabolism.
The hormone stimulates protein anabolism in liver by:
(i) Enhancing the transport of amino acids to liver from extra-hepatic tissues,
(ii) Enhancing ribosomal translation of different proteins. Glucocorticoid may promote urea synthesis in liver by stimulating the activities of different urea cycle enzymes like arginase, arginosuccinate synthase etc.
(3) Effects on lipid metabolism:
Cortisol increases the mobilisation of fatty acids and glycerol from adipose tissue in the blood and making them available for gluconeogenesis. It decreases the retention of fat in adipose tissue. It enhances adipose tissue lipolysis by inducing the activity of the rate-limiting enzyme triacylglycerol lipase. The action of Cortisol may stimulate appetite and the laying down of additional fat in the central or truncal areas.
(4) Effects on calcium metabolism:
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Glucocorticoids markedly reduce intestinal calcium absorption, which tends to lower serum calcium. It also increases urinary calcium excretion. Hypercalciurea is consistent feature of Cortisol excess. Glucocorticoid may directly stimulate PTH (Parathyroid hormone) release that, in turn, stimulates bone resorption.
(5) Effects on growth and development:
Glucocorticoids accelerate the development of a number of systems and organs in foetal and differentiating stages though the mechanisms are not clear.
(6) Effects on circulatory system:
The steroids have little effect on erythropoiesis and hemoglobin concentration. But the hormones influence both leukocyte movement and function. These steroids increase the number of intravascular polymorphonuclear leukocytes and decrease the migration of inflammatory cells to sites of injury. Glucocorticoids also decrease lymphocyte production and functions of these cells.
(7) Effects on cardiovascular system:
Glucocorticoids may stimulate cardiac output and increase peripheral vascular tone, possibly by augmenting the effects of other vasoconstrictors, e.g. the catecholamines. These hormones in excess may cause hypertension independently of their mineralocorticoid effects.
(8) Renal function:
These steroids affect water and electrolyte balance. Thus, corticosteroids such as betamethasone may increase sodium and water excretion.
(9) Central nervous system function:
Glucocorticoids readily enter the brain and can alter behaviour and cognitive functions.
(10) Inflammatory and Immunologic effects:
Glucocorticoids suppress inflammation and immune responses.
These hormones show anti-inflammatory effects by:
(i) Blocking the release of lysosomal hydrolases;
(ii) Decreasing vascular permeability to prevent extravasation of fluids into tissues;
(iii) Decreasing the number of circulating monocytes, eosinophils and lymphocytes;
(iv) Reducing the migration of leukocytes into tissues and their aggregation in the affected area;
(iv) Inhibiting the proliferation of fibroblasts and collagen synthesis;
(v) Preventing histamine release from mast cell granules;
(vi) Inhibiting the synthesis of kinins, interleukin-I
(vii) Increasing the transcription of genes coding for anti-inflammatory proteins including lipocortin-I, interleukin-10 and neutral endopeptidase.
The immunosuppressive effects of glucocorticoids are exhibited by:
(i) Decreased synthesis of proteins and decreased antigen- induced proliferation of lymphocytes in thymus, lymph glands and spleen;
(ii) Stimulation of lysis of specific lymphocytes and
(iii) Reduced T-cell mediated immunity.
Role # 2. Mineralocorticoids:
Mineralocorticoids perform important roles in mineral ion transport and electrolyte balance in several ways.
(1) Sodium retention:
Aldosterone increases active sodium reabsorption and decreases the elimination of Na+ in urine, sweat, saliva and gastric juice. This action is highest in the distal convoluted tubules and collecting tubules of kidney.
It increases the number of Na+ channels in the luminal membrane of target cells, thus enhancing the membrane permeability to Na+. This in turn increases the passive diffusion of Na+ down its inward electrochemical gradient from the duct lumen into the cells through the Na+ channels.
The hormone promotes ATP formation to drive the sodium pump which actively extrudes Na+ from the cell to the interstitial fluid, maintaining a low intracellular Na+ concentration and enhancing thereby the passive inward diffusion of Na+ from luminal fluid into the cells.
(2) Elimination of potassium:
Aldosterone facilitates the passive transfer of potassium from tubular cells into the urine. Aldosterone over secretion is accompanied by K+ diuresis, hypokalemia. Due to stimulated activity of Na+-K+ pump in renal tubular cells and other epithelial cells, K+ may be actively pumped into the cells from the interstitial fluid across the membrane in exchange of Na+, K+ may then diffuse passively into the luminal fluid across the apical membrane of the cells. The hormone also stimulates the formation of K+ channels in the luminal plasma membrane of target cells.
(3) Water retention:
In renal tubules aldosterone increases Na+ reabsorption which secondarily enhances the osmotic reabsorption of water from the urine.
Role # 3. Adrenal Androgens:
The direct biological activity of the adrenal androgens is minimal, and these steroids primarily function as precursors for peripheral conversion to the active androgenic hormones like testosterone and dihydrotestosterone.
Effects in males:
In normal males, the conversion of adrenal androstenedione to testosterone accounts for less than 5% of the production rate of this hormone and thus, the physiological effect is negligible. However, in boys, it causes premature penile enlargement and early development of secondary sexual characteristics.
Effects in females:
In females, androgen production is substantially contributed by peripheral conversion of adrenal androstenedione. In the follicular phase of the menstrual cycle, adrenal precursor accounts for two-thirds of testosterone production. During mid-cycle, the ovarian contribution increases, the adrenal precursor accounts for only 40% of testosterone production.
In females, adrenal androgen overproduction results in some abnormalities manifested by acne, hirsutism and virilization. In the latter case, an involution of female secondary sex characters and their replacement by male accessory sex characters is observed.