Effects of Azoles on the In vitro Follicular Steroidogenesis in Amphibians

摘要

Azoles are widely used antifungal agents, which inhibit the biosynthesis of fungal cell-membrane ergosterol. In this study, using an amphibian follicle culture system, the effects of azoles on follicular Steroidogenesis in frogs were examined. Itraconazole (ICZ), clotrimazole (CTZ) and ketoconazole (KCZ) suppressed pregnenolone (P_5) production by the follicles (ED_(50); 0.04 mu M, 0.33 mu M, and 0.91 mu M, respectively) in response to frog pituitary homogenates (FPH). However, fluconazole (FCZ), miconazole (MCZ) and econazole (ECZ) were not effective in the suppression of P_5 production. Not all the azoles examined suppressed the conversion of exogenous P_5 to progesterone (P_4) (by 3(3-HSD) or P_4 to 17 alpha-hydroxyprogesterone (17 alpha-OHP) (by17 alpha-hydroxylase), or androstenedione (AD) to testosterone (T) (by 17 beta-HSD). In contrast, CTZ, MCZ and ECZ in medium partially suppressed the conversion of 17 alpha-OHP to AD (by C_(17-20) lyase) (ED_(50); 0.25 mu M, 4.5 mu M, and 0.7 mu M, respectively) and CTZ, KCZ, ECZ and MCZ strongly suppressed the conversion of exogenous T to estradiol (E_2) (by aromatase) (ED_(50); 0.02 mu M, 8 mu M, 0.07 mu M, 0.8 mu M, respectively). These results demonstrated that some azole agents strongly suppress amphibian follicular Steroidogenesis and particularly, P450scc and aromatase are more sensitive to azoles than other steroidogenic enzymes.