Inhibitor specificity of the placental microsomal oxidase system responsible for the aromatization of epitestosterone (17 alpha-hydroxy-4-androsten-3-one).
Human placental microsomes converted epitestosterone to estradiol-17 alpha at rates of 23-48 pmol/min X mg protein with a Km of 113 microM. Activity was inhibited 70-90% by concentrations of CO, metyrapone, n-octylamine, 7,8-benzoflavone and 7-ethoxycoumarin which had no effect on the aromatization of 4-androstene-3, 17-dione. Conversely, cyanide and azide were more effective inhibitors of the conversion of the latter androgen. A variety of neutral steroids inhibited the aromatization of epitestosterone with 19-norsteroids being particularly effective, but competitive effects could not be demonstrated. Both 17 beta-hydroxy-4-estren-3-one and 16 alpha-hydroxy-4-androstene-3,17-dione caused a mixed inhibition. A number of phenolic steroids were also inhibitory with 16-oxo compounds being particularly effective. Inhibition by estrone was non-competitive (Ki = 16 microM). The aromatization of epitestosterone resembles placental microsomal oxidase activities against estrone and benzo [a]pyrene in its inhibitor specificity and epitestosterone may be the native substrate for an oxidase also active in the metabolism of aromatic xenobiotic chemicals.
D001141:Aromatase / Q000378:metabolism*; D004845:Epitestosterone / Q000378:metabolism; D004958:Estradiol / Q000096:biosynthesis; D004970:Estrone / Q000378:metabolism; D005260:Female; D006420:Hemeproteins / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008861:Microsomes / Q000201:enzymology*; D010088:Oxidoreductases / Q000378:metabolism*; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013250:Steroid Hydroxylases / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology
D006420:Hemeproteins; D008024:Ligands; D013256:Steroids; D004970:Estrone; D004845:Epitestosterone; D004958:Estradiol; D010088:Oxidoreductases; D013250:Steroid Hydroxylases; D001141:Aromatase