NOVEL MECHANISMS UNDERLYING THE TRANSSYNAPTIC CONTROL OF LHRH RELEASE

LHRH 释放的跨突触控制的新机制

• 批准号: 8357725
• 负责人: Sergio R Ojeda
• 金额: $ 3.63万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357725
• 关键词: Adult; Amenorrhea; Communication; Competence; Family; Female; Funding; Genes; Glutamates; Gonadotropin Hormone Releasing Hormone; Grant; Human; Hypothalamic structure; Ion Transport; Kallmann Syndrome; Mediating; National Center for Research Resources; Nature; Neuroglia; Neurons; Periodicity; Play; Primates; Principal Investigator; Proteins; Regulation; Regulatory Element; Reproduction; Research; Research Infrastructure; Resources; Role; Signal Pathway; Source; Synapses; Syndrome; Testing; United States National Institutes of Health; cost; gamma-Aminobutyric Acid; member; novel; reproductive

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 除了神经胶质细胞到神经元的信号通路外，黄体生成素释放激素 (LHRH) 的分泌还受到兴奋性和抑制性突触输入的控制。利用 γ 氨基丁酸 (GABA) 进行突触通讯的神经元为 LHRH 神经元网络提供主要的抑制输入。我们进行了研究，以确定这些调节成分可能对女性成年期 LHRH 神经元的功能产生的影响。测试的假设是：1）直接作用于 LHRH 神经元的兴奋性 GABAAR 介导的输入是正常生殖周期所必需的，2）离子转运控制蛋白的新型 FXYD 家族成员在 LHRH 分泌的调节中发挥作用，3） Nell2 是一种在谷氨酸能神经元中特异性表达的新基因，是谷氨酸能控制繁殖所需的上游调控元件，4) 一种称为 Nell2 的新基因C14ORF4 在协调生殖周期的双重兴奋/抑制性跨突触控制中发挥作用。从这些研究中得出的概念预计将增加我们对人类综合征（例如下丘脑闭经和特发性下丘脑性腺功能减退症）生殖能力丧失背后的细胞机制的理解。