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Comparative Effects of Ketoconazole on Rat, Dog and Human Testicular Steroidogenesis

1989; Volume: 2; Issue: 4 Linguagem: Inglês

10.3109/14756368909088479

8755-5093

R. De Coster, M C Coene, C. van Camp, K. Van Camp, D. Beerens, W Cools,

Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Ketoconazole is an antifungal azole derivative which also inhibits the cytochrome P-45017α, catalyzing the conversion of progestins into androgens. The effects of ketoconazole on human, dog and rat testosterone biosynthesis were compared using short term incubations of dispersed testicular cells. The results showed that ketoconazole inhibited androgen biosynthesis at lower concentrations in dispersed human testicular cells (IC50: 0.08μmol/l) than in canine (IC50: 0.1μmol/l) and rat cells (IC50 ±0.2μmol/l). Furthermore, they demonstrated that ketoconazole first inhibited the 17,20-lyase activity and then the 17-hydroxylation in rat and dog cells whereas only the 17-hydroxylation was affected in human cells.