Effects of ketoconazole on rat testicular steroidogenic enzymatic activities.
Ketoconazole (K) is an antifungal imidazole derivative which has been shown to be a potent inhibitor of testosterone (T) biosynthesis in rodents and humans. To study the effect of K on rat testicular steroidogenesis we measured the activities of five testicular microsomal steroidogenic enzymes in K-treated rats and controls. Thirty male adult rats were given either 2 mg K or water every 12 hours by mouth during 5 days. Mean testicular weight was similar in both groups of animals. The K-treated group had a T serum concentration of 83 +/- 14 ng/dL whereas it was 94 +/- 16 ng/dL in the control group (NS). The K-treated animals had decreased activities of the 3 beta-hydroxysteroid dehydrogenase (830 +/- 48 vs 2,245 +/- 109 pmol/mg protein/min, P less than 0.001), 17-hydroxylase (243 +/- 5 vs 676 +/- 17 pmol/mg protein/min, P less than 0.001), 17-ketosteroid reductase (31 +/- 2 vs 169 +/- 7 pmol/mg protein/min, P less than 0.001), and aromatase enzymes (92 +/- 6 vs 123 +/- 7 pmol/mg protein/min, P less than 0.01). The 17,20-desmolase activity was similar in both groups of animals (210 +/- 4 vs 171 +/- 18 pmol/mg protein/min). We conclude that K given orally to rats inhibits the activity of several testicular steroidogenic enzymes.
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000446:Aldehyde-Lyases / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D066298:In Vitro Techniques; D007654:Ketoconazole / Q000494:pharmacology*; D008297:Male; D008861:Microsomes / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D013256:Steroids; D015067:17-Hydroxysteroid Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; D001141:Aromatase; D013254:Steroid 17-alpha-Hydroxylase; D000446:Aldehyde-Lyases; D007654:Ketoconazole