The Metabolism and Mechanism of Action of Aldosterone*

ALTHOUGH the clinical importance of the adrenal cortex in the regulation of electrolyte balance had long been realized (1), it was not until the early 1950s that the major regulatory steroid, aldosterone, was isolated and identified by Simpson et al. (2). Simpson and Tait used a sensitive mineralocorticoid bioassay based on changes of urinary 24Na/42K ratios in adrenalectomized rats to help isolate aldosterone (3). Aldosterone is still the most potent mineralocorticoid known: 30–50 times more potent than deoxycorticosterone and at least a thousand times more active than the glucocorticoids, cortisol and corticosterone. Aldosterone's greater potency is balanced by a reduced secretory rate compared with most other adrenal steroids (4, 5). Its synthesis, exclusively by the zona glomerulosa of the adrenal cortex, is responsive to dietary sodium and potassium manipulations and more acutely to ACTH, plasma potassium concentrations, and the renin-angiotensin system (5, 6). Many of the initial investigations were undertaken principally to study regulation of the secretion of aldosterone in normal and pathophysiological conditions.