Inhibitor specificity of the placental microsomal oxidase system responsible for the aromatization of epitestosterone (17α-hydroxy-4-androsten-3-one)

Human placental microsomes converted epitestosterone to estradiol-17α at rates of 23–48 pmol/min-mg protein with a Km of 113 μM. 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 17β-hydroxy-4-estren-3-one and 16α-hydroxy-4-androstene-3,17-dione caused a mixed inhibition. A number of phenolic steroids were also inhibitory with 16-oxo compounds being particulary effective. Inhibition by estrone was non-competitive (Ki = 16 μM). 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.