NEUROENDOCRINOLOGY OF PUBERTY AND SEXUAL DEVELOPMENT

这项提议的目的是对发展中的 生殖下丘脑的成熟过程 因此，女性青春期的开始。利用老鼠作为动物 模型，实验被用来检验大脑的假说 神经营养因子调节下丘脑LHRH的发育 分泌系统，当释放LHRH时达到顶峰 会引发第一次排卵前促性腺激素激增。为此， 提出了以下具体目标。 1.证明神经生长因子(NGF)和 转化生长因子α(TGFα)及其各自的 受体，在下丘脑表达，并检查它们的 对LHRH分泌的发育调节有贡献。 2.检验关于转化生长因子α促进形态变化的假设 和LHRH神经元的功能分化，并确定NGF 对LHRH神经元和/或调节LHRH的神经系统具有营养作用 功能。 3.检验下丘脑营养因子的假设，并在 尤其是表皮生长因子受体EGFR/TGFα配基系统 可通过直接调节转录水平影响LHRH的合成 LHRH基因的活性。 4.验证TGFα是神经营养因子之一的假说 促进青春期周围性腺非依赖性激活的因素 释放LHRH。 这些目标的实现有赖于一个人的团队参与 神经内分泌学家，一名分子生物学家和两名形态学家，以及 论神经内分泌、神经生物学和分子生物学的综合应用 接近了。

The proposal is aimed at gaining new insight into the developmental processes that underlie the maturation of the reproductive hypothalamus and, hence, the onset of female puberty. Utilizing the rat as the animal model, experiments are proposed to examine the hypothesis that brain neuronotrophic factors regulate the development of the hypothalamic LHRH- secreting system, which culminates when a discharge of LHRH release triggers the first preovulatory surge of gonadotropins. To this end, the following specific aims are proposed. 1. To document the hypothesis that nerve growth factor (NGF) and transforming growth factor alpha (TGFalpha), as well as their respective receptors, are expressed in the hypothalamus, and to examine their contribution to the developmental regulation of LHRH secretion. 2. To examine the hypothesis that TGFalpha facilitates the morphological and functional differentiation of LHRH neurons and to determine whether NGF is trophic for LHRH neurons and/or a neuronal system regulatory to LHRH function. 3. To examine the hypothesis that hypothalamic trophic factors, and in particular the epidermal growth factor receptor EGFr/TGFalpha ligand system can influence LHRH synthesis by directly regulating transcriptional activity of the LHRH gene. 4. To examine the hypothesis that TGFalpha is one of the neuronotrophic factors that contribute to the peripubertal, gonadal-independent activation of LHRH release. The accomplishment of these aims depends on the team participation of one neuroendocrinologist, one molecular biologist, and two morphologists, and on the integrated use of neuroendocrine, neurobiology and molecular biology approaches.