Effects of ketoconazole on rat testicular steroidogenic enzymatic activities

Abstract

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 micro-somal 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 β-hydroxysteroid dehydrogenase (830 ± 48 vs 2, 245 ± 109 pmol/mg protein/min, P < 0.001), 17-hydroxylase (243 ± 5 vs 676 ± 17 pmol/mg protein/min, P < 0.001), 17-ketosteroid reductase (31 ± 2 vs 169 ± 7 pmol/mg protein/min, P < 0.001), and aromatase enzymes (92 ± 6 vs 123 ± 7 pmol/mg protein/ min, P < 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.