Effects of ketoconazole on rat ovarian steroidogenic enzymatic activities.
Ketoconazole (K) is an antifungal imidazole derivative which is a potent inhibitor of steroid biosynthesis in rodents and humans. To study the effect of K on rat ovarian steroidogenesis we measured the activities of five ovarian microsomal steroidogenic enzymes in K-treated rats and controls. Thirty hypophysectomized, gonadotropin-treated female adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean ovarian weight was similar in both groups of animals. The K-treated group had an estradiol (E) serum concentration of 176 +/- 48 pg/ml whereas it was 278 +/- 56 pg/ml in the control group (NS). The K-treated animals had decreased activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes. The 3 beta hydroxysteroid-dehydrogenase and 17-hydroxylase activities were similar in both groups. We conclude that K directly inhibits the activities of the 17,20-desmolase, 17-ketosteroid-reductase and aromatase enzymes in the rat ovary.
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D005260:Female; D007016:Hypophysectomy; D007654:Ketoconazole / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology*; D010053:Ovary / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*
D013256:Steroids; D004958:Estradiol; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme; D007654:Ketoconazole