Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.
Role of endogenous opiates in the expression of negative feedback actions of androgen and estrogen on pulsatile properties of luteinizing hormone secretion in man.
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内源性阿片在雄激素和雌激素对人类黄体生成素分泌的脉动特性的负反馈作用表达中的作用。
DOI：
10.1172/jci111417
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发表时间：
1984
期刊：
影响因子：
--
通讯作者：
Ertel,NH
中科院分区：
文献类型：
--
作者：
Veldhuis,JD;Rogol,AD;Samojlik,E;Ertel,NH
我们已经测试了参与内源性阿片途径的负反馈作用的性腺类固醇激素的黄体生成素（LH）的释放在正常男性的脉动特性。为此，性类固醇激素静脉输注的剂量，在稳态条件下选择性抑制频率或幅度的脉动LH信号。通过计算机分析12小时观察期间连续采血获得的LH系列，定量评估脉冲式LH分泌的特性。当纯（nonaromatizable）雄激素，5-α-二氢睾酮，连续输注108小时的血液生成率的睾酮，我们能够实现选择性抑制LH脉冲频率类似于在实验动物中观察到的低剂量雄激素替代。在这些条件下，睾酮和雌二醇-17 β的血清浓度没有显著变化，但血清5 α-二氢睾酮浓度增加约2 - 3倍，其主要代谢产物5 α-雄甾烷-3 α，17 β-二醇的水平相应增加。在单独的实验中，雌二醇-17 β在其血液生产率超过4.5天的间隔输注选择性抑制LH脉冲幅度，而不影响LH脉冲频率。雌激素输注可使血清雌二醇-17 β水平增加约2倍，而不显著改变血液雄激素浓度。然后，我们使用这些时间表的选择性雄激素或雌激素输注，调查参与的内源性阿片类药物在个人的抑制性反馈作用的纯雄激素或雌激素对脉冲式LH释放，通过管理一个强大的和特定的阿片受体拮抗剂，纳曲酮，在输注。我们的观察结果表明，尽管连续输注一定剂量的5 α-二氢睾酮显著抑制LH脉冲频率，但联合使用阿片受体拮抗剂可有效地将LH脉冲频率恢复至对照水平。此外，在输注抑制剂量的雌二醇-17 β期间，阿片受体阻断剂显著增加LH脉冲频率并将LH峰值幅度增加至对照水平。因此，目前在正常男性中的研究首次证明，阿片受体阻滞剂可有效拮抗纯雄激素对LH脉冲频率的选择性抑制作用。这一关键性的观察结果表明，阿片能和雄激素依赖性机制特异性和协调地控制下丘脑促性腺激素释放激素（GnRH）脉冲发生器。
We have tested the participation of endogenous opiate pathways in the negative feedback actions of gonadal steroids on pulsatile properties of luteinizing (LH) hormone release in normal men. To this end, sex steroid hormones were infused intravenously at dosages that under steady state conditions selectively suppressed either the frequency or the amplitude of the pulsatile LH signal. The properties of pulsatile LH secretion were assessed quantitatively by computerized analysis of LH series derived from serial blood sampling over 12 h of observation. When the pure (nonaromatizable) androgen, 5-alpha-dihydrotestosterone, was infused continuously for 108 h at the blood production rate of testosterone, we were able to achieve selective inhibition of LH pulse frequency akin to that observed in experimental animals after low-dosage androgen replacement. Under these conditions, serum concentrations of testosterone and estradiol-17 beta did not change significantly, but serum 5 alpha-dihydrotestosterone concentrations increased approximately two- to threefold, with a corresponding increase in levels of its major metabolite, 5 alpha-androstan-3 alpha, 17 beta-diol. In separate experiments, the infusion of estradiol-17 beta at its blood production rate over a 4.5-d interval selectively suppressed LH pulse amplitude without influencing LH pulse frequency. Estrogen infusion increased serum estradiol-17 beta levels approximately twofold without significantly altering blood androgen concentrations. We then used these schedules of selective androgen or estrogen infusion to investigate the participation of endogenous opiates in the individual inhibitory feedback actions of pure androgen or estrogen on pulsatile LH release by administering a potent and specific opiate-receptor antagonist, naltrexone, during the infusions. Our observations indicate that, despite the continuous infusion of a dosage of 5 alpha-dihydrotestosterone that significantly suppresses LH pulse frequency, co-administration of an opiate-receptor antagonist effectively reinstates LH pulse frequency to control levels. Moreover, during the infusion of a suppressive dose of estradiol-17 beta, opiate receptor blockade significantly augments LH pulse frequency and increases LH peak amplitude to control levels. Thus, the present studies in normal men demonstrate for the first time that the selective inhibitory action of a pure androgen on LH pulse frequency is effectively antagonized by opiate-receptor blockade. This pivotal observation indicates that opiatergic and androgen-dependent mechanisms specifically and coordinately control the hypothalamic pulse generator for gonadotropin-releasing hormone (GnRH)Images
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DOI：
--
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DOI：
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期刊：
Federation proceedings
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