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内源性阿片肽调节雄激素对正常女性下丘脑-垂体轴的抑制作用。

Endogenous opioids modulate the inhibitory effects of androgen on the hypothalamic-pituitary axis of normal women.

作者信息

Vermesh M, Silva P D, Lobo R A

机构信息

Department of Obstetrics and Gynecology, University of Southern California School of Medicine, Los Angeles.

出版信息

J Clin Endocrinol Metab. 1987 Dec;65(6):1183-6. doi: 10.1210/jcem-65-6-1183.

DOI:10.1210/jcem-65-6-1183
PMID:3680480
Abstract

This study was designed to investigate the effect of dihydrotestosterone (DHT) on LH secretion in normal women and the role of endogenous opioids in modulating this effect. Pulsatile LH release and maximum LH responsiveness to exogenous GnRH were determined on 3 consecutive days: basally (day 1), during DHT infusion (day 2), and during DHT plus naloxone (Nal) infusion (day 3). Steady state plasma DHT levels of 6.5 +/- 1.1 (+/- SEM) ng/mL (22.5 +/- 3.8 nmol/L) were achieved by infusion. DHT infusion significantly decreased the maximum LH response to GnRH from 35.5 +/- 8.2 to 11.6 +/- 2.8 IU/L (P less than 0.05). This inhibitory effect was not altered by Nal. In addition, DHT significantly decreased LH pulse frequency (basal, 4.3 +/- 0.3; DHT, 2.8 +/- 0.3 pulses/6 h; P less than 0.05), but not the amplitude of the LH pulses. However, after the addition of Nal to DHT, the pulse frequency increased significantly from 2.8 +/- 0.3 to 4.7 +/- 0.3 pulses/6 h (P less than 0.05). The mean plasma LH level did not change during the infusion of DHT alone, but it did increase significantly when Nal was added (DHT, 4.8 +/- 1.0; DHT + Nal, 7.9 +/- 1.0 IU/L; P less than 0.01). The results of this acute pharmacological study suggest that androgens may have two separate effects on the hypothalamic-pituitary axis: 1) inhibition of GnRH release, which appears to be mediated via opioid peptides, and 2) inhibition of pituitary LH secretion, which is not dependent on opioids.

摘要

本研究旨在调查二氢睾酮(DHT)对正常女性促黄体生成素(LH)分泌的影响以及内源性阿片类物质在调节此效应中的作用。连续3天测定LH的脉冲式释放以及对外源性促性腺激素释放激素(GnRH)的最大LH反应:基础状态(第1天)、DHT输注期间(第2天)以及DHT加纳洛酮(Nal)输注期间(第3天)。通过输注使稳态血浆DHT水平达到6.5±1.1(±标准误)ng/mL(22.5±3.8 nmol/L)。DHT输注使对GnRH的最大LH反应从35.5±8.2显著降至11.6±2.8 IU/L(P<0.05)。这种抑制作用未被Nal改变。此外,DHT显著降低LH脉冲频率(基础状态,4.3±0.3;DHT,2.8±0.3次脉冲/6小时;P<0.05),但不改变LH脉冲的幅度。然而,在DHT中加入Nal后,脉冲频率从2.8±0.3显著增加至4.7±0.3次脉冲/6小时(P<0.05)。单独输注DHT期间平均血浆LH水平未改变,但加入Nal时显著升高(DHT,4.8±1.0;DHT+Nal,7.9±1.0 IU/L;P<0.01)。这项急性药理学研究结果表明,雄激素可能对下丘脑 - 垂体轴有两种不同的作用:1)抑制GnRH释放,这似乎是通过阿片肽介导的;2)抑制垂体LH分泌,这不依赖于阿片类物质。

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