Inhibition of ovarian aromatase by ketoconazole.
In an in vitro system, ketoconazole inhibited the aromatization of [4-14C]-testosterone to estradiol-17 beta by rat ovarian tissue, in a dose-related manner. The amount of an intermediate, 4-androsten-17 beta, 19-diol-3-one, formed was also reduced. When the latter steroid or a subsequent intermediate, 4-androsten-19-aldehyde-3, 17-dione, was used as substrate, ketoconazole at approximately three times the molar concentration of the substrate, depressed estradiol-17 beta synthesis to 38% and 66% of control respectively. With ketoconazole in a concentration of about thirty times that of the substrate, estradiol-17 beta synthesis was depressed to approximately 10% that of control. It is concluded that ketoconazole inhibits all three sequential hydroxylation steps leading to the ovarian aromatization of androgens.
D000818:Animals; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000096:biosynthesis; D005260:Female; D007654:Ketoconazole / Q000494:pharmacology*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013739:Testosterone / Q000378:metabolism
D047072:Aromatase Inhibitors; D013739:Testosterone; D004958:Estradiol; D007654:Ketoconazole