physiology

mineralocorticoids

Mineralocorticoids are a group of steroid hormones produced by the adrenal gland in its outermost portion, called cortical or adrenal cortex; therefore they represent a sub-category of corticosteroids. The division of these hormones on a functional basis in fact sees the mineralocorticoids - active on the hydromineral metabolism - divided into a second category, that of glucocorticoids, active on the metabolism of glucose. Furthermore, while the mineralocorticoid synthesis takes place in the glomerular (more external) area of ​​the cortex, glucocorticoids are produced in the fasciculate and reticular zone (more internal).

As anticipated, the mineralocorticoids regulate the water and salt exchange, retaining sodium and water at the kidney level, and favoring the elimination of potassium and hydrogenions through an active secretion process.

As a result, they increase the plasma volume (volume) and consequently the arterial pressure.

Like all steroid hormones, mineralocorticoids exert their action through binding to a specific receptor (in this case a cytoplasmic receptor for mineralocorticoids), which at nuclear level influences the expression of responsive genes. This rather slow mechanism of action is flanked by a more rapid biochemical pathway, mediated by the interaction of mineralocorticoids with special membrane receptors, whose activation triggers a cascade of intracellular signals.

The affinity of aldosterone to the cytoplasmic receptor of mineralocorticoids is analogous to that of cortisol, an important glucocorticoid that circulates in the body at levels about 100 times higher; its mineralocorticoid activity is, however, inhibited by the 11 β-hydroxysteroid dehydrogenase (11 β-HSD) enzyme, which converts cortisol to cortisone, greatly diminishing its affinity for the cytoplasmic receptors of mineralocorticoids. Licorice, and in particular its active ingredient, glycyrrhizic acid, can inhibit the activity of this enzyme, inducing a state of hyper-pseudo-aldosteronism in the body (although aldosterone levels are normal, the clinical picture suggests an underlying rise in the same).

The mineralocorticoid activity is maximum for aldosterone and its precursors (11-deoxycorticosterone and 18-hydroxy-11-deoxycorticosterone), while it is decidedly lower - but certainly not negligible - for glucocorticoids such as cortisol and cortisone, and for other hormones, like progesterone. We are therefore talking, as already explained, of a subdivision in functional terms prevailing.

Among the drugs with high mineralocorticoid activity, we recall fludrocortisone, which unlike aldosterone also has an important glucocorticoid action. For therapeutic purposes, mineralocorticoids are used in the treatment of Addison's disease and in severe hypotensive states.

The mineralocorticoid synthesis undergoes the important influence of the renin-angiotensin system. Renin is produced by the juxtaglomerular cells of the renal arterioles (particularly sensitive to changes in blood pressure and also subjected to sympathetic control) and acts on angiotensinogen (protein of hepatic origin) transforming it into angiotensin. On the latter then another enzyme acts, called ACE (angiotensin converting enzyme), expressed in the lungs, endothelial cells and plasma. Angiotensin II thus originates, which in the perspective of a global hypertensive effect, also stimulates the secretion of aldosterone.

The system just illustrated is stimulated by hypovolemia, hyposodemia and hypotension.

The secretion of aldosterone is also regulated by the blood levels of sodium and potassium, as well as by a pituitary factor called ASF ( Aldosterone Stimulating Factor ) and by the adrenocorticotropic hormone (ACTH), always of pituitary origin, which nonetheless plays a marginal role. An inhibitory effect on aldosterone release is instead exerted by the atrial natriurethral factor, a peptide hormone secreted by atrial myocardial cells in response to distension of the right atrium wall induced by hypervolemia (excessive increase in blood volume).