Prenatal testosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in the developing sheep.
Prenatal testosterone differentially masculinizes tonic and surge modes of luteinizing hormone secretion in the developing sheep.
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产前睾酮在发育中的绵羊中使黄体生成素分泌的强直和激增模式差异雄性化。
DOI：
10.1159/000127010
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发表时间：
1995
影响因子：
4.1
通讯作者：
Foster,DL
中科院分区：
文献类型：
--
作者：
Wood,RI;Mehta,V;Herbosa,CG;Foster,DL
在绵羊中，在性别分化的关键时期出生前暴露于雄激素可以使补充性黄体生成素(LH)分泌雄性化，并使黄体生成素高峰消失。本研究调查了这两种促黄体生成素分泌模式可能的独立控制，正如它们的发育历史所揭示的那样。具体地说，我们测试了这一假设，即紧张型和波浪型黄体生成素的雄激素化存在不同的临界期。每周给怀孕的母羊注射西柏酸睾丸酮(200毫克油)。作为对照，为了诱导生殖神经内分泌功能的男性化，一组雌性大鼠在妊娠30天至86天期间接受了睾酮治疗(长组)。为了确定强直性黄体生成素分泌的阳性化是否独立于黄体生成素高峰，另外两组在第30-51天(早期组)或65-86天(晚期组)接受治疗。出生时，长期和早期治疗的女性外生殖器男性化；晚期治疗组的外生殖器正常。在2周龄时，所有雄性雌性动物，以及正常雄性和雌性(n=8)，被摘除性腺，并用充满雌二醇的硅胶胶囊替代类固醇。首先，为了确定青春期类固醇敏感性下降的时间，每周监测两次循环黄体生成素。其次，在9月龄雌二醇急剧升高后，每隔1-2小时测量一次黄体生成素，持续60小时，以检验黄体生成素峰系统的功能。在强的促黄体生成素分泌方面，对照组雄性和长期用药的雌性分别在7.1±0.3周龄和10.9±1.7周龄出现强的促黄体生成素持续增加(平均值±SE)。对照组雌鼠强直促黄体生成素在27.1±0.8周时升高。尽管他们的生殖器不同，但早期和晚期的睾酮治疗产生了中间效应：黄体生成素分泌分别在19.3±1.2周和20.4±0.8周增加。在雌激素刺激下，所有对照雌鼠均产生黄体生成素高峰，在激素治疗后18.4±0.6h达到峰值。对于对照男性和长期治疗的女性，在整个60小时的采样期内，黄体生成素浓度不会持续高于未抑制的治疗前水平。18只早、晚期用药的雌鼠中，除4只外，其余雌鼠对雌二醇刺激均有反应，黄体生成素峰值分别在29.8±1.6h和31.8±1.3h，显著晚于对照组。这些数据表明，在不阻止黄体生成素高峰的情况下，可以促进青春期强直性黄体生成素分泌的增加，从而提示强直性黄体生成素分泌和高峰黄体生成素分泌可以被产前的睾丸素区别地男性化。
In sheep, prenatal exposure to androgens during a critical period for sexual differentiation can masculinize tonic luteinizing hormone (LH) secretion and defeminize the LH surge. The present study investigated the possible independent control of these two modes of LH secretion, as revealed by their developmental history. Specifically, we tested the hypothesis that separate critical periods exist for androgenization of tonic and surge LH secretion. Pregnant ewes were treated weekly with testosterone cypionate (200 mg in oil). As a control and to induce robust masculinization of reproductive neuroendocrine function, one group of females received testosterone from day 30 to 86 of gestation (LONG group). To determine if masculinization of tonic LH secretion develops separately from that of the LH surge, two additional groups were treated from day 30 to 51 (EARLY group) or 65-86 (LATE group). At birth, the external genitalia of the LONG- and EARLY-treated females were masculinized; those of the LATE-treated group were normal. At 2 weeks of age, all androgenized females, together with normal males and females (n = 8 each), were gonadectomized and steroids replaced using an estradiol-filled Silastic capsule. First, to determine the timing of the pubertal decrease in steroid sensitivity, circulating LH was monitored twice weekly. Second, to test the function of the LH surge system, LH was measured every 1-2 h for 60 h after an acute increase in estradiol at 9 months of age. With regard to tonic LH secretion, in control males and LONG-treated females, a sustained increase in tonic LH in the presence of constant steroid feedback occurred at 7.1 ± 0.3 and 10.9 ± 1.7 weeks of age, respectively (mean ± SE). In control females, tonic LH increased at 27.1 ± 0.8 weeks. Despite the differences in their genitalia, EARLY and LATE testosterone treatment produced intermediate effects: LH secretion increased at 19.3 ± 1.2 and 20.4 ± 0.8 weeks, respectively. In response to acute estradiol stimulation, all control females produced a surge of LH that peaked 18.4 ± 0.6 h after steroid treatment. For the control males and LONG-treated females, LH concentrations were not sustained above unsuppressed pretreatment levels throughout the 60-hour sampling period. All but 4 of the 18 EARLY- and LATE-treated females responded to estradiol stimulation with a surge of LH that peaked at 29.8 ± 1.6 and 31.8 ± 1.3 h, significantly later than that of control females. These data indicate that it is possible to advance the pubertal increase in tonic LH secretion without preventing the LH surge, thereby suggesting that tonic and surge LH secretion can be differentially masculinized by prenatal testosterone.