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产前双氢睾酮使绵羊促黄体生成素分泌的紧张性和脉冲式模式出现不同的雄性化。

Prenatal dihydrotestosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in sheep.

作者信息

Masek K S, Wood R I, Foster D L

机构信息

Department of Biology, University of Michigan, Ann Arbor 48109-0404, USA.

出版信息

Endocrinology. 1999 Aug;140(8):3459-66. doi: 10.1210/endo.140.8.6913.

DOI:10.1210/endo.140.8.6913
PMID:10433201
Abstract

The control of LH secretion in sheep is sexually differentiated. Males begin to reduce their sensitivity to inhibitory steroid feedback, leading to a pubertal increase in tonic LH secretion by 10 weeks of age, but females remain hypersensitive until 30 weeks. Moreover, only females can respond to the positive feedback action of estradiol to produce a preovulatory LH surge. Prenatal exposure of the female lamb to testosterone masculinizes tonic LH and abolishes the LH surge postnatally. However, the type of steroid involved is not known because testosterone can be converted to estradiol or dihydrotestosterone (DHT). This study tested the hypothesis that DHT, which cannot be converted to an estrogen, masculinizes tonic LH without defeminizing the LH surge. Pregnant ewes were treated with DHT (800, 400, or 200 mg/week) during the critical period for sexual differentiation of gonadotropin secretion (days 30-90; 145 days is term). To evaluate the time of the decrease in responsiveness to steroid inhibition, a constant steroid feedback signal was produced. At 4 weeks of age, androgenized females (800 mg, n = 5; 400 mg, n = 4; 200 mg, n = 5) and control males (n = 7) and females (n = 9) were gonadectomized and implanted with a SILASTIC brand estradiol capsule. Tonic LH secretion in males began to increase at 6.7 +/- 0.5 weeks (mean +/- SEM). In DHT-treated females, the LH increase began at the same time (800 mg DHT, 10.7 +/- 3.9 weeks; 400 mg DHT, 9.9 +/- 5.9 weeks; 200 mg DHT, 7.1 +/- 4.9 weeks). This was several months earlier than in control females (29.1 +/- 0.8 weeks; P < 0.05). After puberty, estradiol induced LH surges in 8 of 9 control females and 11 of 12 DHT-treated females, but not in any control males. These results lead to the hypothesis that in the sheep, distinct requirements exist for differentiation of 2 types of reproductive hormone control systems, and that conversion of testosterone to an estrogen is not essential for both. Aromatization is necessary to prevent the surge control of GnRH from operating in the male, but nonaromatizable androgens differentiate the tonic control to permit high GnRH secretion earlier in life.

摘要

绵羊促黄体生成素(LH)分泌的控制存在性别差异。雄性在10周龄时开始降低对抑制性类固醇反馈的敏感性,导致青春期时LH的基础分泌增加,但雌性在30周龄之前一直保持高敏感性。此外,只有雌性能够对雌二醇的正反馈作用作出反应,从而产生排卵前LH峰。雌性羔羊在产前暴露于睾酮会使其LH基础分泌男性化,并在出生后消除LH峰。然而,由于睾酮可转化为雌二醇或双氢睾酮(DHT),所以所涉及的类固醇类型尚不清楚。本研究检验了以下假设:不能转化为雌激素的DHT可使LH基础分泌男性化,而不会使LH峰女性化特征消失。在促性腺激素分泌性分化的关键时期(第30 - 90天;孕期145天),对怀孕母羊用DHT(800、400或200mg/周)进行处理。为了评估对类固醇抑制反应性降低的时间,产生了一个恒定的类固醇反馈信号。在4周龄时,对雄激素化的雌性(800mg,n = 5;400mg,n = 4;200mg,n = 5)以及对照雄性(n = 7)和雌性(n = 9)进行性腺切除,并植入SILASTIC品牌的雌二醇胶囊。雄性的LH基础分泌在6.7±0.5周时开始增加。在DHT处理的雌性中,LH的增加在同一时间开始(800mg DHT,10.7±3.9周;400mg DHT,9.9±5.9周;200mg DHT,7.1±4.9周)。这比对照雌性(29.1±0.8周)早几个月(P < 0.05)。青春期后,雌二醇在9只对照雌性中的8只以及12只DHT处理雌性中的11只中诱导出LH峰,但在任何对照雄性中均未诱导出。这些结果引出了以下假设:在绵羊中,两种类型的生殖激素控制系统的分化存在不同的要求,并且睾酮向雌激素的转化对于两者并非都是必需的。芳香化作用对于防止GnRH的高峰控制在雄性中起作用是必要的,但不可芳香化的雄激素可使基础控制分化,从而使GnRH在生命早期分泌增加。

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