The effects of adrenal and gonadal steroids and K+-canrenoate on the metabolism of aldosterone by rat liver microsomes.
The synthesis of polar aldosterone metabolites by rat liver microsomes at physiological concentrations of aldosterone (21.5 nM), was markedly inhibited by progesterone, testosterone, corticosterone, K+-canrenoate and estradiol-17 beta. In contrast, corticosterone and estradiol-17 beta significantly increased the synthesis of reduced aldosterone metabolites by 8- and 15-fold respectively, the majority of which were 5 alpha-reduced products of aldosterone. In experiments at higher substrate (aldosterone) concentrations (20-200 microM) the synthesis of ring A-reduced aldosterone metabolites by liver microsomes followed Michaelis-Menten kinetics with a Km[app] for aldosterone of 160 microM and Vmax[app] of 12.2 nmoles/mg protein/5 min. In these experiments progesterone, testosterone and K+-canrenoate all competitively inhibited the synthesis of reduced metabolites with inhibition constants (Ki [app]) of 70, 85 and 55 microM respectively; however, corticosterone did not. In contrast, estradiol-17 beta increased the rate of synthesis of reduced products by 40%, lowering the Km[app] to 83 microM.
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002191:Canrenoic Acid / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003345:Corticosterone / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D011245:Pregnadienes / Q000494:pharmacology*; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000494:pharmacology
D012739:Gonadal Steroid Hormones; D011245:Pregnadienes; D013739:Testosterone; D000450:Aldosterone; D011374:Progesterone; D004958:Estradiol; D002191:Canrenoic Acid; D003577:Cytochrome P-450 Enzyme System; D003345:Corticosterone