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 t estosterone secretion and testicular interstitial fluid (TIF) formatio n through measurement of serum LH, serum testosterone, TIF testosteron e, and TIF volumes. Imidazole, 1-methylimidazole, 4-methylimidazole (4 -MI), and ketoconazole, an oral imidazole antifungal agent, caused dos e-dependent decreases in testosterone secretion and TIF formation. Imi dazole, 2-methylimidazole, and 4-MI decreased LH secretion. 4-MI decre ased testosterone secretion 1-6 h after injection, increased testoster one 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 s timulatory effects of hCG on testosterone secretion and prevented an e xpected increase in LH secretion after the 4-MI-induced decrease in te stosterone secretion. 4-MI also reversed the effects of three other st imulants of testosterone secretion that presumably act through three d ifferent testicular regulatory systems: N-methyl-D,L-aspartate, an exc itatory amino acid; N-G-nitro-L-arginine methyl eater, a nitric oxide synthase inhibitor; and naltrexone, an opioid antagonist. These result s support the hypothesis that imidazoles inhibit testicular function a nd male reproductive function through inhibition of testosterone secre tion, TIF formation, and LH secretion regulatory systems.