Imidazoles Suppress Rat Testosterone Secretion and Testicular Interstitial Fluid Formation In Vivo

The aim of these studies was to examine the effects of imidazoles on testosterone secretion and testicular interstitial fluid (TIF) formation through measurement of serum LH, serum testosterone, TIF testosterone, and TIF volumes. Imidazole, 1-methylimidazole, 4methylimidazole (4-MI), and ketoconazole, an oral imidazole antifungal agent, caused dose-dependent decreases in testosterone secretion and TIF formation. Imidazole, 2-methylimidazole, and 4-MI decreased LH secretion. 4-MI decreased testosterone secretion 1 -6 h after injection, increased testosterone at 8-16 h, decreased LH secretion at 4 h, decreased TIF volumes at 1-8 h, and slightly increased TIF volumes at 24 h. 4-MI blocked the stimulatory effects of hCG on testosterone secretion and prevented an expected increase in LH secretion after the 4-MI-induced decrease in testosterone secretion. 4-MI also reversed the effects of three other stimulants of testosterone secretion that presumably act through three different testicular regulatory systems: N-methyl-D,L-aspartate, an excitatory amino acid; NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor; and naltrexone, an opioid antagonist. These results support the hypothesis that imidazoles inhibit testicular function and male reproductive function through inhibition of testosterone secretion, TIF formation, and LH secretion regulatory systems.