A system biology approach to identify regulatory pathways underlying the neuroendocrine control of female puberty in rats and nonhuman primates.
A system biology approach to identify regulatory pathways underlying the neuroendocrine control of female puberty in rats and nonhuman primates.
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DOI：
10.1016/j.yhbeh.2012.09.013
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发表时间：
2013-07
影响因子：
3.5
通讯作者：
Ojeda, Sergio R.
中科院分区：
文献类型：
--
作者：
Lomniczi, Alejandro;Wright, Hollis;Castellano, Juan Manuel;Sonmez, Kemal;Ojeda, Sergio R.
关键词：
青春期是一个重要的发育里程碑，受遗传因素和环境因素（主要是代谢和昼夜节律性质）的相互作用控制。下丘脑神经分泌神经元增加的十肽促性腺激素释放激素（GnRH）的脉冲式释放是青春期过程开始和进展所必需的。这种增加是由与GnRH神经元相关的神经元和神经胶质网络中发生的协调变化引起的。这些变化最终导致GnRH神经元网络的神经元和神经胶质刺激输入增加，跨突触抑制影响减少。虽然已经使用以基因为中心的方法确定了一些控制青春期GnRH分泌的主要参与者，但对整个过程的系统范围控制知之甚少。由于青春期GnRH释放的激活涉及多种细胞表型，以及无数的细胞内和细胞间信号分子，因此似乎整个过程是由高度协调和相互作用的调控系统控制的，该系统涉及数百个（如果不是数千个）基因产物。在这篇文章中，我们将讨论新出现的证据表明，这些基因被安排为功能连接的网络组织，内部和跨子网络，在一个层次的方式。根据这一概念，这些网络的核心是由转录调节因子组成的，通过指导下游从属基因的表达，为参与启动青春期过程的细胞网络提供稳定性和协调。这些基因网络对外部输入的整合反应被假定为通过表观遗传机制来协调。
Puberty is a major developmental milestone controlled by the interaction of genetic factors and environmental cues of mostly metabolic and circadian nature. An increased pulsatile release of the decapeptide gonadotropin releasing hormone (GnRH) from hypothalamic neurosecretory neurons is required for both the initiation and progression of the pubertal process. This increase is brought about by coordinated changes that occur in neuronal and glial networks associated with GnRH neurons. These changes ultimately result in increased neuronal and glial stimulatory inputs to the GnRH neuronal network and a reduction of transsynaptic inhibitory influences. While some of the major players controlling pubertal GnRH secretion have been identified using gene-centric approaches, much less is known about the system-wide control of the overall process. Because the pubertal activation of GnRH release involves a diversity of cellular phenotypes, and a myriad of intracellular and cell-to-cell signaling molecules, it appears that the overall process is controlled by a highly coordinated and interactive regulatory system involving hundreds, if not thousands, of gene products. In this article we will discuss emerging evidence suggesting that these genes are arranged as functionally connected networks organized, both internally and across sub-networks, in a hierarchical fashion. According to this concept, the core of these networks is composed of transcriptional regulators that, by directing expression of downstream subordinate genes, provide both stability and coordination to the cellular networks involved in initiating the pubertal process. The integrative response of these gene networks to external inputs is postulated to be coordinated by epigenetic mechanisms.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
DOI：
10.1073/pnas.1834399100
发表时间：
2003-09-16
影响因子：
11.1
作者：
de Roux, N;Genin, E;Milgrom, E
通讯作者：
Milgrom, E
DOI：
10.1375/1369052042335278
发表时间：
2004-10-01
期刊：
TWIN RESEARCH
影响因子：
--
作者：
Eaves, L;Silberg, J;Worthman, C
通讯作者：
Worthman, C
影响因子：
30.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.1107533108
发表时间：
2011-09-20
影响因子：
11.1
作者：
Clasadonte, Jerome;Poulain, Pierre;Prevot, Vincent
通讯作者：
Prevot, Vincent