Inhibition of ovarian aromatase by ketoconazole
Watanabe, H.; Menzies, J.A.
Research Communications in Chemical Pathology and Pharmacology 54(2): 181-189
1986
ISSN/ISBN: 0034-5164 PMID: 3786945 Document Number: 272826
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, depreseed 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.