FGF Regulation of GnRH Neurons

促性腺激素释放激素(GnRH)是一种神经激素，负责 生殖的激活和维持。合成GnRH的神经元必须 在开发过程中经历复杂的成熟过程才能成为功能 能够支持复制的系统。一旦成熟，GnRH系统还需要 在适当的时间内保持功能，以确保后代的繁殖。 因此，一个人的生殖健康严重依赖于协调 GnRH系统的形成和维护。拟议研究的目标是 了解一组信号分子、成纤维细胞生长因子(FGFs)和 它们的受体(FGFRs)调节发育成熟和出生后 GnRH系统的功能。一些转基因小鼠模型，每个模型都缺乏 成纤维细胞生长因子信号系统的一个独特的组成部分，将被用来研究这些 缺陷导致GnRH系统的异常形成或维持， 最终导致不孕不育。体外培养方法、形态分析、基因 将利用表情研究、电生理学和整个动物操作来 这就是目的。这项研究与公共卫生高度相关，因为一种 许多FGFRs会导致以生殖障碍为特征的人类疾病。 了解FGFs和FGFRs如何调节GnRH系统可以提供 对这些人的GnRH系统破坏的性质的重要见解。在……里面 此外，它还将揭示编码FGFs/FGFRs的其他基因的突变是否也是 这些人类疾病的候选者。

Gonadotropin-releasing hormone (GnRH) is a neurohomrone responsible for the activation and maintenance of reproduction. Neurons that synthesize GnRH must undergo complex maturational processes during development to become a functional system capable of supporting reproduction. Once mature, the GnRH system also needs to remain functional for an appropriate duration to ensure the propagation of offspring. Thus, one's reproductive health is critically dependent on factors that orchestrate the formation and maintenance of the GnRH system. The goal of the proposed study is to understand how a group of signaling molecules, fibroblast growth factors (FGFs), and their receptors (FGFRs) regulate the developmental maturation and postnatal functionality of the GnRH system. A number of transgenic mouse models, each lacking a distinct component of the FGF signaling system, will be used to investigate if these deficiencies result in the aberrant formation or maintenance of the GnRH system, ultimately leading to sterility. In vitro culture methods, morphological analysis, gene expression studies, electrophysiology, and whole animal manipulation will be utilized for this purpose. This research is highly relevant to public health because mutations on one of the FGFRs lead to human disorders characterized by reproductive failure. Understanding how FGFs and FGFRs regulate the GnRH system could provide important insights into the nature of GnRH system disruption in these individuals. In addition, it will reveal if mutations on other genes encoding FGFs/FGFRs are also candidates for these human disorders.