NEUROENDOCRINE CONTROL OF FEMALE PUBERTY

女性青春期的神经内分泌控制

• 批准号: 8357726
• 负责人: Sergio R Ojeda
• 金额: $ 5.82万
• 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/8357726
• 关键词: Affect; Brain; Cell Communication; Cells; Communication; Competence; Epidermal Growth Factor; Family; Female; Funding; Genes; Genomics; Gonadotropin Hormone Releasing Hormone; Grant; Growth Factor; Hormones; Human; Hypothalamic structure; Mediating; Mutant Strains Mice; National Center for Research Resources; Nervous system structure; Neuraxis; Neuroglia; Neurons; Neurosecretory Systems; Play; Primates; Principal Investigator; Process; Proteins; Proteomics; Puberty; Regulatory Pathway; Research; Research Infrastructure; Resources; Role; Sexual Development; Source; Syndrome; System; United States National Institutes of Health; cost; 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. 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.

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。 这些研究探讨了大脑内细胞间通讯在控制女性青春期中所起的作用。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）之间的相互通讯对于女性及时获得性成熟至关重要和生殖能力。我们已经确定了这种胶质神经元调节系统的几个组成部分，并阐明了它们用来将信息从星形胶质细胞转移到分泌黄体生成素释放激素（LHRH）的神经元（LHRH是控制女性性发育的激素）的一些细胞间机制。与表皮生长因子 (EGF) 蛋白质相关的生长因子家族被发现由星形胶质细胞产生，并相互作用促进 LHRH 分泌，从而调节青春期过程的启动。使用突变小鼠，其中这些介导 EGF 相关蛋白作用的关键识别分子的正常功能受损，我们证明这些星形胶质细胞衍生的生长因子是正常女性性发育所必需的。我们还使用基因组和蛋白质组学方法来鉴定在下丘脑中表达的参与青春期过程控制的新基因。总而言之，这些结果支持了这样的概念：人类性早熟和性发育迟缓的综合征可能与影响这些主要调节途径的异常有关。