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青春期成熟早期编程与破坏的动物模型

Animal Modeling of Early Programming and Disruption of Pubertal Maturation.

作者信息

Castellano Juan M, Tena-Sempere Manuel

出版信息

Endocr Dev. 2016;29:87-121. doi: 10.1159/000438877. Epub 2015 Dec 17.

DOI:10.1159/000438877
PMID:26680574
Abstract

Puberty is a fascinating developmental transition that gates the attainment of reproductive capacity and culminates the somatic and sexual maturation of the organism. Rather than a circumscribed phenomenon, puberty is the endpoint of a long-lasting developmental continuum, which initiates in utero. Besides important genetic determinants, the tempo of puberty is influenced by numerous endogenous and exogenous factors that, acting at different levels of the developing hypothalamic-pituitary-gonadal (HPG) axis along the maturational continuum indicated above, can influence puberty onset. Among the different modifiers of puberty, in this chapter we will focus our attention on two major groups of signals, sex steroids and nutritional cues, and how these interplay mostly with the central elements of the HPG axis, and especially with gonadotropin-releasing hormone neurons and their key upstream afferents, Kiss1 neurons, to influence the timing of puberty. Special emphasis will be given to summarize information emerging from relevant preclinical (mostly rodent) animal models, and how this information might be relevant in terms of translational medicine, as it may help for a better understanding and eventually management of pubertal disorders of escalating prevalence worldwide.

摘要

青春期是一个迷人的发育转变过程,它开启了生殖能力的获得,并使机体的躯体和性成熟达到顶点。青春期并非一种局限的现象,而是一个始于子宫内的长期发育连续过程的终点。除了重要的遗传决定因素外,青春期的节奏还受到众多内源性和外源性因素的影响,这些因素沿着上述成熟连续过程作用于发育中的下丘脑 - 垂体 - 性腺(HPG)轴的不同水平,从而能够影响青春期的启动。在青春期的不同调节因素中,在本章我们将重点关注两大类信号,即性类固醇和营养信号,以及它们如何主要与HPG轴的中枢元件相互作用,特别是与促性腺激素释放激素神经元及其关键的上游传入神经元Kiss1神经元相互作用,以影响青春期的时间。我们将特别强调总结来自相关临床前(主要是啮齿动物)动物模型的信息,以及这些信息在转化医学方面可能具有的相关性,因为它可能有助于更好地理解并最终管理全球范围内患病率不断上升的青春期疾病。

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