title: The effects of adrenal and gonadal steroids and K+-canrenoate on the metabolism of aldosterone by rat liver microsomes.
abstract: 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.
mesh_terms: 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
chemical_list: 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