NEUROENDOCRINE CONTROL OF FEMALE PUBERTY

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。 这些研究检查了大脑中细胞间的通讯在控制女性青春期中所起的作用。目前正在发展的概念是，神经元（中枢神经系统的两个主要功能和结构单位之一）和星形胶质细胞（神经系统的另一个主要组成部分）之间的相互交流对于及时获得女性性成熟和生殖能力至关重要。我们已经确定了几个组成部分，这种神经胶质细胞的调节系统，并阐明了一些细胞间的机制，他们采用的信息从星形胶质细胞的神经元分泌促黄体生成素释放激素（LHRH），激素控制女性性发育。与称为表皮生长因子（EGF）的蛋白质相关的生长因子家族被发现由星形胶质细胞产生，并相互作用以促进LHRH分泌，从而调节青春期过程的开始。使用突变小鼠，其中这些关键的识别分子介导的EGF相关蛋白的行动的正常功能受损，我们证明了这些星形胶质细胞衍生的生长因子是正常的女性性发育所需的。我们还使用基因组和蛋白质组学的方法，以确定新的基因，在下丘脑中表达，参与控制青春期的过程。总之，这些结果提供了支持的概念，即性早熟和延迟性发育的综合征在人类的中央起源可能与影响这些主要的调节途径的异常。

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. These studies examine the role that cell-cell communication within the brain plays in the control of female puberty. The concept is being developed that reciprocal communication between neurons (one of the two main functional and structural units of the central nervous system) and astroglial cells (the other main building block of the nervous system) is critical for the timely acquisition of female sexual maturity and reproductive competence. We have identified several components of this glia-neuron regulatory system and elucidated some of the intercellular mechanisms they employ to transfer information from astroglial cells to the neurons that secrete luteinizing hormone-releasing hormone (LHRH), the hormone controlling female sexual development. A family of growth factors related to a protein known as epidermal growth factor (EGF) was found to be produced by astroglial cells and to function interactively to facilitate LHRH secretion and, thus, regulate the initiation of the pubertal process. Using mutant mice in which the normal function of these pivotal recognition molecules mediating the actions of EGF-related proteins was impaired, we demonstrated that these astroglial-derived growth factors are required for normal female sexual development. We have also used genomic and proteomic approaches to identify new genes that, expressed in the hypothalamus, participate in the control of the pubertal process. Altogether these results provide support for the concept that the syndromes of sexual precocity and delayed sexual development of central origin in humans may be related to abnormalities affecting these major regulatory pathways.