Adrenal corticosteroids aldosterone

Aldosterone, IIfi,21-dihydroxy-3 0-tBaxo-pregn-4-en-18-al-I8 - II hemiacelal a highly active mineralocorticoid from the adrenal cortex. Unlike other hormones of the adrenal cortex, A. has a carbonyl group on Cl 8, which forms a hemiacetal with the llp-hydroxyl group. It is the most important mineralocorticoid, regulating NaCl resorption and K excretion. It also has some glucocorticoid activity. For structure and biosynthesis, see Adrenal corticosteroids. 

Glucocorticoids and mineralocorticoids are uniquely produced by the adrenal cortex, and are collectively termed corticosteroids. Apart from aldosterone, glucocorticoid secretion is regulated by the pituitary hormone, corticotrophin. The principal corticosteroids synthesized in the body are illustrated in Figure 1.6. Glucocorticoids generally exhibit weak mineralocorticoid actions and vice versa. 

Pregnenolone leaves the mitochondria to become the obligatory precursor of corticosteroids and adrenal androgens. The biosynthetic pathway next branches into two separate routes. One route passes through progesterone and corticosterone to aldosterone, and the other... 

These conditions are associated with high renin and high aldosterone production. The hybrid corticosteroids 18-OHF, 18-oxo-F and 18-oxo-THF were isolated from the urine of a patient with adrenal adenoma by Ulick and coworkers [11]. These steroids were subsequently also shown to be dominant in GRA. Their formation in the latter condition was explained by Lifton and co-workers [51] with the discovery of a chimeric gene formed crossover of the 1 1//-hydroxylase (CYPllfil) and aldosterone synthase (CYP11B2) genes. 

Thus, in patients with Addison s disease or other forms of adrenal insufficiency, continuing oral administration of cortisone acetate or fludrocortisone acetate enables salt balance to be restored. Other corticosteriods and analogues that have been used in the hormonal control of sodium levels include aldosterone and deoxycortone acetate. Individual corticosteroids vary in the extent to which they possess the various hormonal activities so that combination therapy is usually required if, for example, mineral balances are to be maintained when corticosteroids are administered for their anti-inflammatory, antirheumatic or anti-allergic properties. 

The adrenal cortex synthesizes corticosteroids (glucocorticoids and mineralocor-ticoids), which differ in activities. In humans, cortisol is the main glucocorticoid, and aldosterone is a main mineralocorticoid. Steroid therapy causes severe potential side effects, hence a careful consideration is always exercised before starting therapy. These are used in variety of disorders such as rheumatic disorder, renal disease, allergic manifestation, bronchial asthma, skin diseases, infectious diseases, malignancy, and hepatic diseases. 

Adrenocorticotropic hormone derives from the anterior pituitary in response to the leptin-or stress-induced anorexigenic, hypothalamic CRH. Corticotropin (like enkephalins and MSHs) derives from a precursor polypeptide pro-opiomelanocortin. Corticotropin induces the catabolic adrenal cortex corticosteroid cortisol and the mineralocorticoid aldosterone (Chapter 11) and is an important regulator of immune responses including chemotaxis and phagocytosis. Corticotropin acts via GPCRs to activate Gas and increase cAMP in anterior pituitary cells. 

Corticotropin stimulates the synthesis of corticosteroids (of which the most important is hydrocortisone) and to a lesser extent of androgens, by the cells of the adrenal cortex. It has only a minor (transient) effect on aldosterone production, which can proceed independently in the absence of corticotropin the cells of the inner cortex atrophy. 

Figure 50-8 The regulatory feedback loop of the hypothalamic-pituitary-adrenal axis. CRH under the influence of neural factors and other modifiable factors that control its pulsatile and circadian secretion acts on the pituitary to produce hormone (ACTH). ACTH in turn stimulates the adrenal gland to form cortisol, aldosterone, dehydroepiandrosterone (DHEA), and androstenedione. Corticosteroids and gamma amino butyric acid (GABA) are inhibitory to CRH and ACTH release, and AVP stimulates ACTH release.

Endocrine hypertension actually includes several diseases characterized by elevated blood pressure with causes that can be traced to an endocrine abnormality or actual injury. Two of the best known are pheochromocytoma and Cushing s syndrome. The former is characterized by a tumor that secretes excessive amounts of catecholamines, primarily epinephrine. This in turn increases vasomotor tone, resulting in a considerable pressure increase. Surgical removal of the tumor is curative. The latter is a disease of the adrenal cortex where tumors may also develop. The cortex is the site of corticosteroid production. Thus excessive production of aldosterone will act on the kidneys, causing retention of sodium and water. This increased blood volume is usually manifested as mild, or sometimes moderate, hypertension. 

CAH is the result of an inherited cnz.yme defect in corticosteroid bio.synthesis. The adrenals cannot secrete cortisol and electrolyte disturbances may involve severe hyponalraemia and hyperkalaemia if aldosterone biosynthesis is also affected. If the condition is not diagnosed quickly the afflicted infant may die. 

ELECTROLYTE AND WATER BALANCE Aldosterone is by far the most potent endogenous corticosteroid with respect to fluid and electrolyte balance. Thus, electrolyte balance is relatively normal in patients with adrenal insufficiency due to pituitary disease, despite the loss of glucocorticoid production by the inner cortical zones. Mineralocorticoids act on the distal tubules and collecting ducts of the kidney to enhance reabsorption of Na+ from the tubular fluid they also increase the urinary excretion of K and H . 

The adrenal cortex produces glucocorticoids (cortisol) and mineralocorticoids (aldosterone). Corticosteroids promote sodium retention and potassium excretion. Corticotropin (Acthar) is an ACTH dmg that is used to diagnosis adrenal gland disorders. 

HT has been found to stimulate corticosteroid secretion in various models. In addition, 5-HT is present in adrenochromaffin cells, but also in mast cells localized at the adrenocortical level [98, 99]. Therefore, 5-HT released within the adrenal gland may have a paracrine effect on corticoid secretion. In- frog and human, the receptor involved in 5-HT induced cortisol secretion displays the pharmacological profile of a typical 5-HT4-R [98, 99]. In human volunteers the aldosterone-stimulating effects were observed after administration of 5-HT4-agonists [137]. 

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