Abstract

The effects of opioids on testicular function were assessed in the rat through measurements of serum testosterone levels, testicular interstitial fluid (TIF) formation and TIF testosterone levels after morphine and opioid antagonist (naloxone, naltrexone) treatment. Serum and TIF levels of testosterone were significantly decreased 1 to 6 h after morphine (10 mg/kg) injection, and TIF volumes were decreased 2-3 h after injection morphine. Each of these decreases was dose-related. In contrast to the effects of morphine, the opioid antagonist naloxone increased TIF testosterone but did not alter TIF volumes. Moreover, the opioid antagonist naltrexone totally blocked morphine's effects on both testosterone secretion and TIF volume, suggesting that morphine's testicular effects were mediated by naltrexone-sensitive opioid receptors in the testes. The possible role of morphine-induced reductions in gonadotropin secretion in morphine's testicular effects was also examined. Morphine suppressed testosterone secretion and TIF volumes after pretreatment with human chorionic gonadotropin, which reverses morphine's suppression of luteinizing hormone (LH). Our results, therefore, indicate that morphine exerts effects on testicular function that are independent of its effects on LH. They furthermore support the hypothesis that both endogenous and exogenous opioids disrupt two major aspects of testicular function: Testosterone secretion and TIF formation. Because of the role of TIF in maintaining testicular function, our results suggest that opioid-induced changes in testosterone secretion into TIF and TIF formation may, at least in part, explain the well-established effects of opioids on reproductive endocrinology and function in the male.