Endogenous opioids participate in the regulation of the hypothalamus-pituitary-luteinizing hormone axis and testosterone's negative feedback control of luteinizing hormone.
Endogenous opioids participate in the regulation of the hypothalamus-pituitary-luteinizing hormone axis and testosterone's negative feedback control of luteinizing hormone.
复制标题
内源性阿片类药物参与下丘脑-垂体-黄体生成素轴的调节以及睾酮对黄体生成素的负反馈控制。
作者：
T. Cicero;B. Schainker;E. Meyer
两种麻醉拮抗剂纳洛酮和纳曲酮在皮下注射后几分钟内显着升高雄性大鼠的血清 LH 水平。注射后 20 分钟，血清 LH 达到峰值。纳洛酮将 LH 水平提高至 1 mg/kg 剂量，此后未发现进一步增加。 0.35 mg/kg 的剂量产生半最大反应。外源性阿片类吗啡以剂量依赖性方式阻断纳洛酮产生的 LH 增加，表明拮抗剂的特异性受体阻断作用可以解释其血清 LH 水平的增强。纳洛酮在下丘脑-垂体-LH 轴内的作用位点似乎位于下丘脑水平，因为该药物对垂体前叶 LHRH 刺激的 LH 释放没有影响，并且在体外不会阻断二氢睾酮对垂体 LH 释放的抑制。纳洛酮还可以防止去势雄性大鼠睾酮对血清 LH 的负反馈抑制。这些研究结果表明，脑组织中存在内源性阿片类药物，通常会抑制下丘脑-垂体-LH 轴的活动，并参与该轴对 LH 产生的雄激素依赖性反馈控制。
Two narcotic antagonists, naloxone and naltrexone, significantly elevated serum LH levels in male rats within minutes after their sc injection. The peak increase in serum LH occurred 20 min after the injection. Naloxone increased LH levels up to a dose of 1 mg/kg, after which no further increases were found. A dose of 0.35 mg/kg produced a half-maximal response. The exogenous opioid morphine blocked the increase in LH produced by naloxone in a dose-dependent fashion, suggesting that the specific receptor-blocking effects of the antagonist could account for its enhancement of serum LH levels. The locus of action of naloxone within the hypothalamic-pituitary-LH axis appeared to be at the level of the hypothalamus since the drug had no effect on LHRH-stimulated release of LH by the anterior pituitary and did not block dihydrotestosterone's suppression of pituitary LH release in vitro. Naloxone also prevented testosterone's negative feedback inhibition of serum LH in the castrated male rat. The results of these studies suggest that endogenous opioids exist in brain tissue which normally inhibit activity in the hypothalamic-pituitary-LH axis and participate in the androgen-dependent feedback control of LH elaboration by this axis.