Aldosterone Biosynthesis, Regulation, and Classical Mechanism of Action

Gordon H. Williams

Circulating aldosterone is principally made in the glomerulosa zone of the adrenal cortex by a series of enzyme steps leading to the conversion of cholesterol to aldosterone. Uniquely, aldosterone's production is regulated at two critical enzyme steps: (1) early in its biosynthetic pathway (the conversion of cholesterol to pregnenolone cholesterol side chain cleavage enzyme) and (2) late (the conversion of corticosterone to aldosterone by aldosterone synthase). A variety of factors modify aldosterone secretion--the most important are angiotensin II (AngII), the end-product of the renin-angiotensin system (RAS), and potassium. However ACTH, neural mediators and natriuretic factors also contribute at least over the short run. Aldosterone's classical epithelial effect is to increase the transport of sodium across the cell in exchange for potassium and hydrogen ions. Although still controversial, there is an increasing body of data that supports the hypothesis that aldosterone can be synthesized in tissues outside of the adrenal cortex, specifically in the heart and the vasculature. Aldosterone's biosynthesis appears to be regulated in these tissues similar to what occurs in the adrenal cortex. The role of this extra adrenal aldosterone production in health and disease is as of yet undetermined.