Clinical Significance And Health Importance On The Actions Of Adrenocorticotropic Hormone (ACTH) On The Adrenal Cortex

The secretion of cortisol occurs only in response to stimulation by ACTH. In health, the levels of cortisol are highest in the morning. Adrenocorticotrophic hormone is reciprocally influenced by plasma levels of cortisol, higher levels inhibit and lower levels stimulate production. It (ACTH) also stimulates the melanocytes and activates tissue lipase. The basic actions of ACTH are as follows:

1. Stimulation and maintenance of growth of the adrenal cortex
2. Activation of adenylcyclase
3. Accumulation of cholesterol
4. Conversion of cholesterol to pregnolone and further steroids.

Pituitary rhythm: Within 2-3 hours of falling asleep, the ACTH levels progressively rise and reach its highest level about an hour or so before waking up. During waking ACTH, levels progressively fall to reach the minimum before falling asleep. The secretion of ACTH and cortisol is increased in response to different stress factors such as trauma, fever, surgery, hypoglycemia, severe anxiety and several others. The circadian rhythm disappears during periods of stress and in adrenal tumours.

About 75% of cortisol circulates in blood bound to transcortin which is a glycoprotein, 15% is lossely bound to albumin and 10% circulates in the free state unbound, and the latter accounts for the metabolic activities of the hormone. When plasma cortisol level is high (e.g. Cushing’s syndrome), plasma transcortin is saturated and the level is unbound cortisol increases. This appears in excessive amounts in urine.

Steroid hormones are inactivated mainly in the liver. Other tissues such as muscles, skin, fibroblasts, intestine and lymphocytes also metabolise them.

Adrenal cortical Hormones: Based on their main functional activity, they can be grouped as glucorcorticoids, mineralocorticoids, and sex hormones (androgens and estrogens). Glucocorticoids are secreted by zona fasciculate, mineralocroticoids are produced by zona glomerulosa and sex hormones are produced by zona reticularis.

Glucocorticoids: The important members of this groups are cortisol (hydrocortisone), corticosterone and 11-dehydrocorticosterone. Normal cortisol level at 9 a.m is 140- 700 nmols/liter (5- 25 ug/dl) and it falls to 0.7ug/liter at midnight.

Glucorcoticoids promote gluconeogenesis and lead to hyperglycemia. Other major effects include increase of protein catabolism, suppression of ACTH, anti-inflammatory and anti-allergic action, immunosuppression and reduction in the size of circulating lymphocyte pool and lymphatic organs (lympholysis). In addition, glucocorticoids exert minor effects such as induction of several enzymes, stimulation of hematopoiesis, fat deposition over the trunk, uricosuria, elimination of a water load, production of a feeling of well- being, reduction in circulating eosinophils and maintenance of the capacity for muscular work. Glucocorticoids are used therapeutically for replacement therapy and in many other conditions. Several synthetic analogues are available for therapeutic use.

Mineralocorticoids: Aldosterone is the most important member in this group, the other comparison of the actions of natural and synthetic corticosteroids.

Beign deoxycorticosterone (DOC), these exert their main action on epithelial membranes of the skin, gastrointestinal tract and Kidney. The main action is conservation of sodium and chloride and elimination of potassium. Excessive activity of these hormones cause retention of sodium and chloride, edema and potassium loss. Aldosterone secretion is stimulated by the rennin angiotensin system. ACTH does not exert any appreciable effect on the secretion of aldosterone.

Renin angiotension system: Renin is stored in the form of granules mainly in the modified cells of the afferent arterioles of the glomeruli. Stimuli such as depletion of extracellular volume, reduction of perfusing pressure of the renal artery, stimulation of sympathetic nerves, and rise in sodium concentration at the macula densa lead to release of rennin. It acts on angiotensinogen to covnert it into angiotension I. Angiotension converting enzyme present in the lungs converts angiotensin I to angiotensin II. Actions of angiotension II include secretion of aldosterone, vascoconstriction, and inhibition of rennin secretion.

Sex hormones: Adrenal cortex secretes sex steroids (both androgens and estrogens) which are small in amount compared to the secretion of the gonads. Under normal conditions, they play only a minor role in the development of secondary sex characters. When the secretion is increased under pathological conditions, they may produce virilisation and less commonly feminization which is more obvious in the male. Adrenal estrogen may lead to gynecomastia in males and precocious puberty in girls. In adult women, excessive secretion of adrenal estrogens leads to amenorrhea and infertility. Secretion of sex hormones is under the control of ACTH.