Opioid modulation of LHRH release in vitro depends upon levels of testosterone in vivo.
Opioid modulation of LHRH release in vitro depends upon levels of testosterone in vivo.
复制标题
阿片类药物对 LHRH 释放的体外调节取决于体内睾酮水平。
作者：
K. Nikolarakis;D. Pfeiffer;O. Almeida;A. Herz
在基础条件下和在灌流介质中加入KCl、阿片拮抗剂纳洛酮或阿片激动剂DAGO后，测定了成年雄性大鼠（完整、去势5天、去势5天后用不同剂量睾酮替代）下丘脑LHRH的体外释放。所有治疗组的下丘脑对56 mM KCl有反应，LHRH输出增加。纳洛酮（10（-6）M）也能诱导LHRH的释放，但仅来自给予生理剂量睾酮的完整体和去势体的组织。阿片受体激动剂DAGO（10（-6）M）不改变LHRH的基础释放，但它能显著降低K+诱导的完整大鼠和用生理水平睾酮替代的大鼠下丘脑LHRH的释放，但对去势大鼠或用少量睾酮替代的去势大鼠下丘脑LHRH的释放无影响。后一种反应的特异性通过其与纳洛酮的可逆性显示。DAGO对低水平类固醇大鼠组织的影响缺乏，这意味着对阿片类影响的反应依赖于类固醇，事实上，当以生理剂量替代睾酮时，对DAGO的反应恢复。下丘脑LHRH含量的测量表明，从完整的，去势和睾酮替代去势大鼠获得的组织之间没有显着差异。这些体外数据支持阿片类药物对LHRH释放的抑制作用取决于体内性腺类固醇的存在的观点。
The in vitro release of LHRH from hypothalami of adult male rats (intact, 5-day castrates, 5-day castrates replaced with various doses of testosterone) was measured under basal conditions and after the addition of KCl, the opiate antagonist naloxone or the opiate agonist DAGO to the perifusion medium. Hypothalami from all treatment groups responded to 56 mM KCl with an increased output of LHRH. LHRH release was also induced by naloxone (10(-6)M), but only from tissues derived from intacts and castrates given physiological doses of testosterone. The opiate agonist DAGO (10(-6)M) did not alter the basal release of LHRH; it, however, caused a significant decrease in the K+-induced release of LHRH from hypothalami derived from intact rats and rats replaced with physiological levels of testosterone but not from those derived from castrate rats or castrate rats replaced with small amounts of testosterone. The specificity of this latter response was shown by its reversibility with naloxone. The lack of DAGO effects upon tissues from rats with low levels of steroid implied steroid dependency of the response to opioidergic influences and indeed, the response to DAGO was restored when testosterone was replaced at physiological doses. Measurement of hypothalamic LHRH content showed no significant differences between tissues obtained from intact, castrate and testosterone-replaced castrate rats. These in vitro data support the view that the inhibitory influence of opioids upon LHRH release depends on the presence of gonadal steroids in vivo.