Hormone, adrenal cortex metabolism

The adrenal cortex produces steroidal hormones that are associated with carbohydrate, fat, and protein metabolism, electrolyte balance, and gonadal functions (58). One of these, cortisone [53-06-5] ( ) demonstrated a remarkable ability to relieve the symptoms of inflammatory conditions... 

Responses to stress by altering blood flow to skeletal muscles and other tissues as well as enhancing secretion of hormones from the adrenal cortex (glucocorticoids) whose metabolic activities enable the body to physically cope with stress... 

The tenn corticosteroids refers to steroid hormones secreted by the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response, and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. 

Mitotane, or o,p -DDD, is an oral medication used in the treatment of adrenocortical carcinoma. Chemically it is an isomere of DDT. Following its metabolism in the adrenal cortex to a reactive acyl chloride intermediate, mitotane covalently binds to adrenal proteins, specitically inhibiting adrenal cortical hormone production. The drug accumulates in fat tissue. It is eliminated mainly by the kidneys with a half-life of 18-159 days. Common side effects include anorexia, nausea, lethargy, sleepiness and skin problems. 

The steroidal nature of adrenocortical hormones was established in 1937, when Reichstein synthesized desoxycorticosterone. Eventually it was clearly established that the adrenal cortex elaborated a number of hormones and that these compounds differed in their amount of inherent metabolic (glucocorticoid) and electrolyte regulating (mineralocorticoid) activity. The actions of these hormones extend to almost every cell in the body. In humans, hydrocortisone (cortisol) is the main carbohydrate-regulating steroid, and aldosterone is the main electrolyte-regulating steroid. 

Corticotropin (adrenocorticotropic hormone, ACTH) regulates the function of the adrenal cortex and has numerous other effects on metabolism. It contains 39 amino acids in the form of a random coil, owing to the presence of several proline residues that prevent helix formation. Species differences are seen in amino acids 25-39 the rest of the ACTH molecule is identical in all animals and humans. The first 24 amino acids are responsible for all of the biological action of ACTH synthetic human ACTHj 24 is known as cosyntropin. 

Hyposecretion of hormones from the adrenal cortex leads to development of Addison s disease which is characterized by loss of appetite, muscular weakness, loss of weight due to loss of water, hypoglycemia, subnormal body temperature, decreased basal metabolic rate, increased blood potassium, decreased blood sodium and inability to maintain the normal protein deposition in the muscles. 

In the animal body three important groups of hormones are formed by the metabolism of cholesterol the progestins, the sex hormones, and the adrenal cortical hormones 249 Their synthesis occurs principally in mitochondria of the adrenal cortex and the gonads. Steroid hormone synthesis is regulated by hormones, such as corticotropin (ACTH), from the anterior pituitary250 (see Chapter 30) and is also dependent upon the recently discovered steroidogenic acute regulatory protein, which in some way promotes the movement of stored cholesterol into mitochondrial membranes.251 252 Some major pathways of... 

Longer lasting control of mineral metabolism is achieved by steroid hormones elaborated by the adrenal cortex and by synthetic analogues. Besides their actions on gluconeogenesis, glycogen deposition, protein metabolism and sexual characteristics, the corticosteriods influence calcium metabolism and the control of water and electrolyte equilibria, so that profound changes accompany their administration. 

The two principal groups of adrenal steroids are the glucocorticoids and mineralocorticoids. These hormones are synthesized from cholesterol within cells of the adrenal cortex. The primary glucocorticoid produced in humans is cortisol (hydrocortisone), and the primary mineralocorticoid is aldosterone. Glucocorticoids exert a number of effects such as regulation of glucose metabolism, attenuation of the inflammatory response, and suppression of the immune system. Mineralocorticoids are involved primarily in the control of fluid and electrolyte balance. 

The mineralocorticoid aldosterone is also produced by the adrenal cortex and promotes retention of H20 and Na+ and loss of K+ by the kidney. Cortisol is also an agonist of the aldosterone receptor but the level of cortisol is kept low by type 2 11 (Thydroxysteroid dehydrogenase, which converts cortisol to the inactive cortisone (11-dehydrocortisol). Accordingly inhibition of this enzyme by 18(i>-glycyrrhetinic acid (from liquorice) elevates cortisol with consequent effects of H20 and Na+ retention, oedema and hypertension. Further potential sites of interference by plant substances with steroid hormone metabolism include enzymes involved in steroid hormone synthesis such as the cytochrome P450-linked 11 -hydroxylase that catalyses the last step of corticosterone synthesis. 

The composition of the excreted urinary 17-ketosleroids also reveals a close similarity between the hormones of different origin the testis accounts for 30% while the adrenal cortex contributes the remaining 70% of the total urinary 17-ketosteroids [383]. Androsterone, ep a-androsterone, and 5/8-androsterone (etiocholanolone) are the main urinary metabolities of testosterone, and dehydroepiandrosterone is the major urinary 17-ketosteroid derived from the adrenal cortex. 

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