Studies of the mechanism through which sodium depletion increases aldosterone biosynthesis in man.

Abstract

Experiments were designed to determine whether Na depletion stimulates the conversion of corticosterone to aldosterone or whether it stimulates the biogenesis of aldosterone precursors. Steroid secretion rates were measured by double isotope dilution derivative methods. To eliminate ACTH-dependent steroid synthesis, the crucial experiments were performed in subjects receiving constant dosage of dexa-methasone. Under these conditions Na depletion caused consistent increases in aldosterone and corticosterone secretion rates without appreciably affecting the cortisol secretion rate. The effect of Na depletion on the adrenal secretion of deoxycorticosterone was measured during continuous administration of both dexamethasone and Metopirone. In subjects receiving dexamethasone, Metopirone, and a low Na diet, deoxycorticosterone secretion rates were consistently higher than when the same subjects received dexamethasone, Metopirone, and a high Na diet. It is concluded that Na depletion stimulates the aldosterone biosynthetic pathway at some step before the formation of deoxycorticosterone so as to increase the availability of aldosterone precursors. This action is relatively specific for the aldosterone pathway and does not appreciably affect the secretion of cortisol. In contrast, small doses of ACTH were shown to stimulate the secretion of cortisol and corticosterone without appreciably affecting the secretion of aldosterone.