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.
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000315:Adrenalectomy; D000450:Aldosterone / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008901:Mineralocorticoids / Q000378:metabolism / Q000494:pharmacology; D009318:Natriuresis / Q000187:drug effects; D011188:Potassium / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine*
D008901:Mineralocorticoids; D000804:Angiotensin II; C013282:tetrahydroaldosterone; D000450:Aldosterone; C018920:5-dihydroaldosterone; D012964:Sodium; D011188:Potassium