Division of Neuroscience, Oregon National Primate Research Center/Oregon, Health & Science University, 505 N.W. 185th Avenue, Beaverton, OR, USA.
Mol Cell Endocrinol. 2010 Aug 5;324(1-2):3-11. doi: 10.1016/j.mce.2009.12.003. Epub 2009 Dec 22.
A sustained increase in pulsatile release of gonadotrophin releasing hormone (GnRH) from the hypothalamus is an essential, final event that defines the initiation of mammalian puberty. This increase depends on coordinated changes in transsynaptic and glial-neuronal communication, consisting of activating neuronal and glial excitatory inputs to the GnRH neuronal network and the loss of transsynaptic inhibitory tone. It is now clear that the prevalent excitatory systems stimulating GnRH secretion involve a neuronal component consisting of excitatory amino acids (glutamate) and at least one peptide (kisspeptin), and a glial component that uses growth factors and small molecules for cell-cell signaling. GABAergic and opiatergic neurons provide transsynaptic inhibitory control to the system, but GABA neurons also exert direct excitatory effects on GnRH neurons. The molecular mechanisms that provide encompassing coordination to this cellular network are not known, but they appear to involve a host of functionally related genes hierarchically arranged. We envision that, as observed in other gene networks, the highest level of control in this network is provided by transcriptional regulators that, by directing expression of key subordinate genes, impose an integrative level of coordination to the neuronal and glial subsets involved in initiating the pubertal process. The use of high-throughput and gene manipulation approaches coupled to systems biology strategies should provide not only the experimental bases supporting this concept, but also unveil the existence of crucial components of network control not yet identified.
下丘脑促性腺激素释放激素 (GnRH) 脉冲释放的持续增加是定义哺乳动物青春期开始的必要的最终事件。这种增加取决于突触间和神经胶质-神经元通讯的协调变化，包括激活 GnRH 神经元网络的神经元和神经胶质兴奋性输入以及突触间抑制性张力的丧失。现在很清楚，刺激 GnRH 分泌的流行兴奋性系统涉及一个由兴奋性氨基酸（谷氨酸）和至少一种肽（ kisspeptin ）组成的神经元成分，以及一个使用生长因子和小分子进行细胞间信号传递的神经胶质成分。GABA 能和阿片能神经元对该系统提供突触间抑制性控制，但 GABA 神经元也对 GnRH 神经元发挥直接兴奋性作用。为这个细胞网络提供全面协调的分子机制尚不清楚，但它们似乎涉及一系列功能相关的基因按层次排列。我们设想，正如在其他基因网络中观察到的那样，该网络的最高控制水平由转录调节剂提供，这些转录调节剂通过指导关键从属基因的表达，对参与启动青春期过程的神经元和神经胶质亚群施加整合水平的协调。高通量和基因操作方法的使用与系统生物学策略相结合，不仅应该提供支持这一概念的实验基础，而且还应该揭示尚未确定的网络控制的关键组成部分的存在。
