NEUROENDOCRINOLOGY OF PUBERTY AND SEXUAL DEVELOPMENT

该提案旨在获得对发展的新见解， 生殖下丘脑成熟的基础过程 也就是女性青春期的开始 利用老鼠作为动物 模型，实验提出了检验的假设，大脑 神经营养因子调节下丘脑LHRH的发育， 分泌系统，当LHRH释放释放时达到高潮 引发排卵前促性腺激素的第一波分泌 为此中央 提出了以下具体目标。 1. 为了证明神经生长因子（NGF）和 转化生长因子α（TGF α），以及它们各自的 受体，在下丘脑中表达，并检查其 促进LHRH分泌的发育调节。 2. 为了检验TGF α促进形态学改变的假设， 和LHRH神经元的功能分化，并确定NGF是否 对LHRH神经元和/或调节LHRH的神经元系统有营养性 功能 3. 为了检验下丘脑营养因子的假设， 特别是表皮生长因子受体EGFr/TGF α配体系统 通过直接调节LHRH的转录水平， LHRH基因的活性。 4. 为了验证TGF α是神经营养因子之一的假设， 促进青春期周围性腺非依赖性激活的因素 LHRH释放 这些目标的实现取决于一个人的团队参与。 神经内分泌学家，一名分子生物学家，两名形态学家， 神经内分泌、神经生物学和分子生物学的综合应用 接近。

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.