Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty
Disentangling puberty: novel neuroendocrine pathways and mechanisms for the control of mammalian puberty
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DOI：
10.1093/humupd/dmx025
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发表时间：
2017-11-01
影响因子：
13.3
通讯作者：
Tena-Sempere, M.
中科院分区：
文献类型：
--
作者：
Avendano, S.;Vazquez, M. J.;Tena-Sempere, M.
背景技术背景：青春期是一个复杂的发育事件，由复杂的调控网络控制，这些网络整合了外周和内部线索，并影响了驱动生殖轴的大脑中心。青春期的克里思是由基因决定的，但也对许多修饰剂敏感，从代谢和性类固醇信号到环境因素。最近的流行病学证据表明，青春期的开始在人类中提前，通过未知的机制。事实上，虽然最近已经收集了许多关于哺乳动物青春期控制机制的知识，但关于负责青春期精确时间及其偏差的亲密分子和神经内分泌途径的基本问题仍然没有解决。目的和依据：通过结合合适的模式物种和人类的数据，我们的目的是提供一个全面的总结，我们目前的理解神经内分泌机制的青春期，特别是集中在其中央调节途径，代谢控制的潜在分子基础和机制。方法：对2003年至2017年发表的文章进行了全面的MEDLINE检索。细胞和动物模型数据（包括我们自己的结果）以及关注哺乳动物青春期病理生理学的临床研究被考虑并与中枢神经内分泌机制、代谢控制和表观遗传/miRNA调节相关的术语交叉引用。在过去十年中进行的研究已经揭示了新的中枢神经内分泌通路在青春期控制中的重要作用，kisspeptins在精确调节青春期GnRH神经分泌活性的激活中具有重要作用。此外，不同的递质，包括神经激肽-B（NKB），可能还有黑皮质素，已经被证明在调节青春期开始时与kisspeptins相互作用。同样，最近的研究也记录了表观遗传机制的作用，主要涉及调节靶向kisspeptins和NKB通路的阻遏物，以及microRNA和相关的结合蛋白Lin 28 B，在青春期的中枢控制中。这些新的途径提供了不同的内源性和环境的线索，包括营养和代谢因素，如瘦素，生长激素释放肽和胰岛素，这是已知的青春期timing.WIDER发挥重要作用青春期的调制青春期的分子和神经内分泌的基础：尽管最近的进展，我们的理解哺乳动物青春期的基础仍然不完整。在这篇综述中总结的新的神经肽能和分子机制的完整阐明不仅将扩大我们对人类青春期发病的亲密机制的认识，而且还可能为更好地预防和管理临床环境中的青春期偏差提供新的工具和目标。
BACKGROUND: Puberty is a complex developmental event, controlled by sophisticated regulatory networks that integrate peripheral and internal cues and impinge at the brain centers driving the reproductive axis. The tempo of puberty is genetically determined but is also sensitive to numerous modifiers, from metabolic and sex steroid signals to environmental factors. Recent epidemiological evidence suggests that the onset of puberty is advancing in humans, through as yet unknown mechanisms. In fact, while much knowledge has been gleaned recently on the mechanisms responsible for the control of mammalian puberty, fundamental questions regarding the intimate molecular and neuroendocrine pathways responsible for the precise timing of puberty and its deviations remain unsolved.OBJECTIVE AND RATIONALE: By combining data from suitable model species and humans, we aim to provide a comprehensive summary of our current understanding of the neuroendocrine mechanisms governing puberty, with particular focus on its central regulatory pathways, underlying molecular basis and mechanisms for metabolic control.SEARCH METHODS: A comprehensive MEDLINE search of articles published mostly from 2003 to 2017 has been carried out. Data from cellular and animal models (including our own results) as well as clinical studies focusing on the pathophysiology of puberty in mammals were considered and cross-referenced with terms related with central neuroendocrine mechanisms, metabolic control and epigenetic/miRNA regulation.OUTCOMES: Studies conducted during the last decade have revealed the essential role of novel central neuroendocrine pathways in the control of puberty, with a prominent role of kisspeptins in the precise regulation of the pubertal activation of GnRH neurosecretory activity. In addition, different transmitters, including neurokinin-B (NKB) and, possibly, melanocortins, have been shown to interplay with kisspeptins in tuning puberty onset. Alike, recent studies have documented the role of epigenetic mechanisms, involving mainly modulation of repressors that target kisspeptins and NKB pathways, as well as microRNAs and the related binding protein, Lin28B, in the central control of puberty. These novel pathways provide the molecular and neuroendocrine basis for the modulation of puberty by different endogenous and environmental cues, including nutritional and metabolic factors, such as leptin, ghrelin and insulin, which are known to play an important role in pubertal timing.WIDER IMPLICATIONS: Despite recent advancements, our understanding of the basis of mammalian puberty remains incomplete. Complete elucidation of the novel neuropeptidergic and molecular mechanisms summarized in this review will not only expand our knowledge of the intimate mechanisms responsible for puberty onset in humans, but might also provide new tools and targets for better prevention and management of pubertal deviations in the clinical setting.