Division of Neuroscience, Oregon National Primate Research Center/Oregon Health and Science University, 505 N.W. 185th Avenue, Beaverton, OR 97006, USA.
Brain Res. 2010 Dec 10;1364:164-74. doi: 10.1016/j.brainres.2010.09.039. Epub 2010 Sep 17.
The initiation of mammalian puberty requires a sustained increase in pulsatile release of gonadotrophin releasing hormone (GnRH) from the hypothalamus. This increase is brought about by coordinated changes in transsynaptic and glial-neuronal communication, consisting of an increase in neuronal and glial stimulatory inputs to the GnRH neuronal network and the loss of transsynaptic inhibitory influences. GnRH secretion is stimulated by transsynaptic inputs provided by excitatory amino acids (glutamate) and at least one peptide (kisspeptin), and by glial inputs provided by growth factors and small bioactive molecules. The inhibitory input to GnRH neurons is mostly transsynaptic and provided by GABAergic and opiatergic neurons; however, GABA has also been shown to directly excite GnRH neurons. There are many genes involved in the control of these cellular networks, and hence in the control of the pubertal process as a whole. Our laboratory has proposed the concept that these genes are arranged in overlapping networks internally organized in a hierarchical fashion. According to this concept, the highest level of intra-network control is provided by transcriptional regulators that, by directing expression of key subordinate genes, impose genetic coordination to the neuronal and glial subsets involved in initiating the pubertal process. More recently, we have begun to explore the concept that a more dynamic and encompassing level of integrative coordination is provided by epigenetic mechanisms.
哺乳动物青春期的启动需要下丘脑促性腺激素释放激素 (GnRH) 的脉冲式释放持续增加。这种增加是通过突触间和神经胶质-神经元通讯的协调变化带来的，包括 GnRH 神经元网络中神经元和神经胶质刺激输入的增加以及突触间抑制影响的丧失。GnRH 的分泌受到兴奋性氨基酸（谷氨酸）和至少一种肽（Kisspeptin）提供的突触间输入以及由生长因子和小生物活性分子提供的神经胶质输入的刺激。对 GnRH 神经元的抑制性输入主要是突触间的，并由 GABA 能和阿片能神经元提供；然而，GABA 也被证明可以直接兴奋 GnRH 神经元。有许多基因参与这些细胞网络的控制，因此也参与整个青春期过程的控制。我们的实验室提出了这样的概念，即这些基因以重叠的网络排列，内部以层次化的方式组织。根据这一概念，网络内的最高级控制由转录调节因子提供，这些调节因子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遗传协调。最近，我们开始探索这样一个概念，即更具动态性和包容性的整合协调水平是由表观遗传机制提供的。
