The possible biological role of aldosterone metabolites

Following the incubation of aldosterone with microsomes from liver of adrenalectomized male rates, a previously unidentified polar neutral metabolite of aldosterone, designated "peak A" material, was isolated and purified using high pressure liquid chromatography. This peak A material, which contains a reduced hydroxylated metabolite of aldosterone, was shown to possess 2% to 3.5% of the mineralocorticoid activity relative to aldosterone. When bovine adrenal glomerulosa cells were incubated with peak A material (3 and 10 micrograms/ml), the binding of 125I-angiotensin II was inhibited by 20% and 36%, respectively. The mineralocorticoid activity of the six possible ring A reduced metabolites was tested. The 5 alpha-reduced metabolites were more potent than the 5 beta-, and the 3 alpha- were more potent than the 3 beta-reduced metabolites. The renal and extrarenal transformations of aldosterone to the polar and nonpolar (reduced) metabolites and their possible role in the accepted mechanism of action of aldosterone is discussed.