NOVEL MECHANISMS UNDERLYING THE TRANSSYNAPTIC CONTROL OF LHRH RELEASE

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 促黄体生成激素释放激素（LHRH）的分泌除了受神经胶质细胞-神经元信号通路的控制外，还受兴奋性和抑制性的跨突触输入的控制。利用γ-氨基丁酸（GABA）进行突触通讯的神经元为LHRH神经元网络提供了主要的抑制性输入。我们已经进行了研究，以确定的影响，这些调节成分可能会施加在女性成年LHRH神经元的功能能力。检验的假设为：1）直接作用于LHRH神经元上的兴奋性GABAAR介导的输入是正常生殖周期所需的，2）离子转运控制蛋白的新FXYD家族的成员在LHRH分泌的调节中起作用，3）Nell 2，一种特异性表达于多巴胺能神经元中的新基因，是多巴胺能控制生殖所需的上游调节元件，和4）一种新的基因C14 ORF 4在协调生殖周期的双重兴奋/抑制跨突触控制中起作用。从这些研究中得出的概念，预计将增加我们对人类综合征，如下丘脑性闭经和特发性下丘脑性腺功能减退症的生殖能力丧失的细胞机制的理解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Luteinizing hormone-releasing hormone (LHRH) secretion is controlled by transsynaptic inputs of both excitatory and inhibitory nature, in addition to glia-to-neuron signaling pathways. Neurons that utilize gamma aminobutyric acid (GABA) for synaptic communication provide the major inhibitory input to the LHRH neuronal network. We have conducted studies to define the impact that these regulatory components may exert on the functional competence of LHRH neurons during female adulthood. The hypotheses tested were: 1) that excitatory GABAAR-mediated inputs exerted directly on LHRH neurons are required for normal reproductive cyclicity, 2) that members of the novel FXYD family of ion transport-controlling proteins play in the regulation of LHRH secretion, 3) that Nell2, a novel gene specifically expressed in glutamatergic neurons, is an upstream regulatory element required for the glutamatergic control of reproduction, and 4) that a novel gene known as C14ORF4 plays a role in coordinating the dual excitatory/inhibitory transsynaptic control of reproductive cyclicity. The concepts derived from these studies are expected to increase our understanding of the cellular mechanisms underlying the loss of reproductive competence in human syndromes such as hypothalamic amenorrhea and idiopathic hypothalamic hypogonadism.