The neuroendocrinology of human puberty revisited
The neuroendocrinology of human puberty revisited
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DOI：
10.1159/000058094
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发表时间：
2002-01-01
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影响因子：
--
通讯作者：
Grumbach, MM
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作者：
Grumbach, MM
哺乳动物下丘脑促黄体生成激素释放激素（LHRH）（1）[1]脉冲发生器-垂体促性腺激素-性腺器官的基本方面具有惊人的共性。然而，不同物种在青春期的神经内分泌方面存在着重要的、实质性的差异。人类青春期的开始以LH脉冲幅度的增加为标志，这是LHRH脉冲幅度增加的间接指标。下丘脑LHRH-垂体促性腺激素复合物在人类胎儿中至少在0.3个妊娠期起作用;胎儿和新生儿LH和FSH分泌模式的性别差异是胎儿睾酮对胎儿下丘脑-垂体-促性腺激素装置的印记的明显结果。直到大约6个月大的男孩和12-24个月大的女孩，睾丸和卵巢通过分泌睾酮和雌二醇分别对男孩的LH和女孩的卵泡刺激素（FSH）的增加做出反应，达到在青春期开始之前不能再次达到的水平。人类下丘脑脉冲发生器的个体发育的显著特征是：（1）它在胎儿期的发育和功能;（2）婴儿期下丘脑LHRH脉冲发生器-垂体促性腺激素轴的持续功能;（3）婴儿晚期下丘脑LHRH振荡器活动的逐渐衰减;（4）儿童期LHRH振荡器活动的静止--所谓的幼年间歇;（5）在儿童晚期，LHRH脉冲发生器的逐渐解除抑制和重新激活，主要在夜间;（6）随着青春期的临近和青春期期间，LHRH脉冲的幅度增加，这反映在循环LH脉冲的逐渐增加和变化的模式中。如Terasawa及其同事在恒河猴中进行的研究所揭示的，负责在儿童期（幼年期）抑制LHRH脉冲发生器的内在中枢神经系统（CNS）机制涉及抑制性神经元系统的主要作用-CNS抑制性神经递质γ-氨基丁酸（GABA）和GABA能神经元。随着青春期的开始，LHRH脉冲发生器的去抑制和再激活与GABA能神经传递的下降以及兴奋性氨基酸神经递质（包括谷氨酸）和可能的星形胶质细胞衍生生长因子的输入的伴随增加有关。尽管在过去的三十年中取得了显着的进展，但我们对控制青春期开始的神经生物学，遗传和环境机制的理解仍然存在很大的差距。本文综述了瘦素在青春期发育调控中的作用。严重的瘦素缺乏症与低促性腺激素性腺功能减退症有关;看来瘦素和瘦素信号的临界水平是达到青春期所必需的。大量的证据支持这样一种假设，即瘦素是几种允许因素之一，而不是人类青春期开始的触发因素。这些进展的应用为性早熟和青春期延迟的分类提供了一个框架。版权所有（C）2002 S. Karger AG.巴塞尔。
The fundamental aspects of the hypothalamic luteinizing hormone-releasing hormone (LHRH)(1) [1] pulse generator-pituitary gonadotrophin-gonadal apparatus in mammals have striking commonalities. There are, however, critical, substantive differences in the neuroendocrinology of puberty among species. The onset of puberty in the human is marked by an increase in the amplitude of LH pulses, an indirect indicator of the increase in amplitude of LHRH pulses. The hypothalamic LHRH-pituitary gonadotrophin complex is functional by at least 0.3 gestation in the human foetus; the sex difference in the fetal and neonatal pattern of LH and FSH secretion is an apparent consequence of imprinting of the fetal hypothalamus-pituitary-gonadotropin apparatus by fetal testosterone. Until about 6 months of age in boys and 12-24 months in girls, the testes and ovaries respond to the increased LH in boys and follicle-stimulating hormone (FSH) in girls by secreting testosterone and oestradiol, respectively, reaching levels that are not again achieved before the onset of puberty, Striking features of the ontogeny of the human hypothalamic pulse generator are: (1) its development and function in the foetus; (2) the continued function of the hypothalamic LHRH pulse generator-pituitary gonadotrophingonadal axis in infancy; (3) the gradual damping of hypo-thalamic LHRH oscillator activity during late infancy; (4) its quiescence during childhood - the so-called juvenile pause; (5) during late childhood the gradual disinhibition and reactivation of the LHRH pulse generator, mainly at night; (6) the increasing amplitude of the LHRH pulses, which are reflected in the progressively increased and changing pattern of circulating LH pulses, with the approach of and during puberty. The intrinsic central nervous system (CNS) mechanisms responsible for the inhibition of the LHRH pulse generator during childhood (the juvenile phase) involve the major role of an inhibitory neuronal system -the CNS inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and GABAergic neurons, as revealed by studies in the rhesus monkey by Terasawa and her associates. With the onset of puberty, the disinhibition and reactivation of the LHRH pulse generator is associated with a fall in GABAergic neurotransmission and a concomitant increase in the input of excitatory amino acid neurotransmitters (including glutamate) and possibly astroglial-derived growth factors. Despite remarkable progress over the past three decades, large gaps remain in our understanding of the neurobiological, genetic and environmental mechanisms involved in the control of the onset of puberty. The role of leptin in the control of the onset of puberty is reviewed. Severe leptin deficiency is associated with hypogonadotrophic hypogonadism; it appears that a critical level of leptin and a leptin signal is required to achieve puberty. The weight of evidence supports the hypothesis that leptin acts as one of several permissive factors and not a trigger in the onset of human puberty. The application of these advances provides a framework for the described classification of sexual precocity and delayed puberty. Copyright (C) 2002 S. Karger AG. Basel.