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生长激素分泌减少会延长青春期,但在没有性腺负反馈的情况下,不会延迟促黄体生成素的发育性增加。

Reduced growth hormone secretion prolongs puberty but does not delay the developmental increase in luteinizing hormone in the absence of gonadal negative feedback.

作者信息

Wilson M E, Chikazawa K, Fisher J, Mook D, Gould K G

机构信息

Yerkes National Primate Research Center, Enory University, 2409 Taylor Lane, Lawrenceville, GA 30043, USA.

出版信息

Biol Reprod. 2004 Aug;71(2):588-97. doi: 10.1095/biolreprod.104.027656. Epub 2004 Apr 28.

Abstract

Previous studies have shown that the growth hormone (GH) axis is important for timing the later stages of puberty in female monkeys. However, it is not clear whether these growth-related signals are important for the initiation of puberty and early pubertal events. The present study, using female rhesus monkeys, used two approaches to answer this question. Experiment 1 tested the hypothesis that reduced GH secretion would blunt the rise in nocturnal LH secretion in young (17 mo; n = 7) but not older adolescent ovariectomized females (29 mo; n = 6). Reduced GH secretion was induced by treating females with the sustained release somatostatin analogue formulation, Sandostatin LAR (625 microg/kg). Morning (0900-0930 h) and evening (2200-2230 h) concentrations of bioactive LH were higher in older adolescent compared to young adolescent females. However, diurnal concentrations were not affected by the inhibition of GH secretion in either age group when compared to the placebo-treated, control condition. Experiment 2 tested the hypothesis that reduced GH secretion induced in young juvenile females would delay the initial increase in nocturnal LH secretion and subsequent early signs of puberty. In order to examine this hypothesis, puberty in control females (n = 7) was compared to those in which puberty had been experimentally arrested until a late adolescent age (29 mo) by the use of a depot GnRH analogue, Lupron (750 microg kg(-1) mo(-1); n = 7). Once the analogue treatment was discontinued, the progression of puberty was compared to a group treated in a similar fashion but made GH deficient by continuous treatment with Sandostatin LAR (n = 6). Puberty occurred as expected in control females with the initial rise in evening LH at 21 mo, menarche at 22 mo, and first ovulation at 30 mo. As expected, Lupron arrested reproductive maturation, but elevations in morning and evening LH and menarche occurred within 2 mo of the cessation of Lupron in both Lupron and Lupron-GH-suppressed females. In contrast, first ovulation was delayed significantly in the Lupron-GH-suppressed females (41 mo) compared to the Lupron-only females (36 mo). These data indicate that within this experimental model, reduced GH secretion does not perturb the early stages of puberty but supports previous observations that the GH axis is important for timing the later stages of puberty and attainment of fertility. Taken together, the data indicate that factors that reduce GH secretion may have a deleterious effect on the completion of puberty.

摘要

以往的研究表明,生长激素(GH)轴对于雌性猴子青春期后期的时间安排很重要。然而,尚不清楚这些与生长相关的信号对于青春期启动和青春期早期事件是否重要。本研究使用雌性恒河猴,采用两种方法来回答这个问题。实验1检验了以下假设:生长激素分泌减少会抑制幼年(17个月;n = 7)而非年龄较大的青春期去卵巢雌性猴子(29个月;n = 6)夜间促黄体生成素(LH)分泌的增加。通过给雌性猴子注射长效生长抑素类似物制剂善龙(Sandostatin LAR,625微克/千克)来诱导生长激素分泌减少。与幼年青春期雌性猴子相比,年龄较大的青春期雌性猴子上午(09:00 - 09:30)和晚上(22:00 - 22:30)生物活性LH的浓度更高。然而,与安慰剂治疗的对照情况相比,两个年龄组中生长激素分泌的抑制均未影响昼夜浓度。实验2检验了以下假设:幼年雌性猴子中诱导的生长激素分泌减少会延迟夜间LH分泌的初始增加以及随后的青春期早期迹象。为了检验这一假设,将对照雌性猴子(n = 7)的青春期与那些通过使用长效促性腺激素释放激素类似物亮丙瑞林(Lupron,750微克·千克⁻¹·月⁻¹;n = 7)实验性地阻止青春期直至青春期后期年龄(29个月)的雌性猴子的青春期进行比较。一旦停止类似物治疗,将青春期进展与以类似方式治疗但通过持续注射善龙而导致生长激素缺乏的一组进行比较(n = 6)。对照雌性猴子的青春期如期出现,晚上LH在21个月时开始增加,初潮在22个月时出现,首次排卵在30个月时出现。正如预期的那样,亮丙瑞林阻止了生殖成熟,但在亮丙瑞林组和亮丙瑞林 - 生长激素抑制组中,上午和晚上LH升高以及初潮在亮丙瑞林停止后的2个月内出现。相比之下,亮丙瑞林 - 生长激素抑制组的雌性猴子首次排卵(41个月)比仅使用亮丙瑞林组(36个月)显著延迟。这些数据表明,在这个实验模型中,生长激素分泌减少不会干扰青春期早期阶段,但支持了以往的观察结果,即生长激素轴对于青春期后期时间安排和生育能力的获得很重要。综上所述,数据表明降低生长激素分泌的因素可能对青春期的完成产生有害影响。

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