NEUROENDOCRINE CONTROL OF FEMALE PUBERTY

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这些研究考察了大脑内的细胞间通讯在女性青春期控制中所起的作用。正在形成的概念是，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)之间的相互通信对于及时获得女性性成熟和生殖能力至关重要。我们已经确定了这个神经胶质细胞-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传递到分泌黄体素的神经元的一些细胞间机制。 激素释放激素(LHRH)，控制女性性发育的激素。与一种被称为表皮生长因子(EGF)的蛋白质有关的一系列生长因子被发现由星形胶质细胞产生，并相互作用，促进LHRH的分泌，从而调节青春期过程的启动。在突变小鼠中，这些关键识别分子介导EGF相关蛋白的正常功能受到损害，我们证明了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方法来识别在下丘脑表达的参与青春期过程控制的新基因。总之，这些结果支持这样的概念，即人类的性早熟和中央起源的性发育延迟的症状可能与影响这些主要调控途径的异常有关。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.