Ultrashortloop Feedback on GnRH Biosynthesis

GnRH 生物合成的超短环反馈

• 批准号: 0315923
• 负责人: Tao-Yiao Wu
• 金额: --
• 依托单位: Henry M Jackson Fdn for Advmt of Military Medicine
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-15 至 2008-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0315923&HistoricalAwards=false
• 关键词: Ultrashortloop; Feedback; GnRH; Biosynthesis

Abstract: The decapeptide gonadotropin-releasing hormone (GnRH) is the central regulator of reproductive function and behavior in mammals. It is secreted from the hypothalamus to induce the release of gonadotropins, which in turn stimulate gonadal function; a preovulatory surge of GnRH release, which coincides with a period of sexual receptivity, culminates in the induction of ovulation. Preliminary results suggest that a metabolic product(s) of GnRH may regulate its biosynthesis as well as induce sexual behavior in the rat. These results lead to the overaching hypothesis that GnRH is important in synchronizing the GnRH surge with the initiation of sexual behavior. This proposal will address one aspect of this hypothesis by determining the mechanism underlying the regulation of GnRH biosynthesis by the metabolite(s). Three specific aims are proposed to determine (1) the GnRH metabolite(s) required to exert a biological action using the GT1-7 cell line as the in vitro model; (2) the involvement of GnRH metabolite(s) in regulating GnRH gene expression in the rat (in vivo); and, (3) the mechanism through which GnRH metabolite(s) regulates GnRH gene expression. Collectively, these studies will use biochemical and molecular biological methods for analysis. It is expected that the results of this proposal will identify the active GnRH metabolite(s) and determine the mechanism by which the metabolite(s) may regulate GnRH gene expression. This is the first study to ascribe a direct biological effect of a metabolic product of GnRH on GnRH gene expression. Successful completion of this proposal will further clarify our understanding of the central regulation of reproductive function in mammals and will pave the way for future studies to determine the mechanism underlying the convergence of the endocrine system with behavior during the preovulatory period. It is anticipated that this project will provide scientific training for a postdoctoral fellow, a graduate student, and college and/or high school students.

摘要：十肽促性腺激素释放激素（GnRH）是哺乳动物生殖功能和行为的中心调节因子。 它由下丘脑分泌，诱导促性腺激素的释放，从而刺激性腺功能；排卵前 GnRH 释放激增，与性接受期一致，最终诱导排卵。 初步结果表明，GnRH 的代谢产物可能调节其生物合成并诱导大鼠的性行为。 这些结果引出了一个重要的假设：GnRH 对于同步 GnRH 激增与性行为的开始很重要。 该提案将通过确定代谢物调节 GnRH 生物合成的潜在机制来解决这一假设的一个方面。 提出了三个具体目标，以确定（1）使用 GT1-7 细胞系作为体外模型发挥生物作用所需的 GnRH 代谢物； (2) GnRH 代谢物参与调节大鼠 GnRH 基因表达（体内）； (3) GnRH 代谢物调节 GnRH 基因表达的机制。 总的来说，这些研究将使用生化和分子生物学方法进行分析。 预计该提案的结果将鉴定活性 GnRH 代谢物并确定代谢物调节 GnRH 基因表达的机制。 这是第一项将 GnRH 代谢产物对 GnRH 基因表达产生直接生物学效应的研究。 该提案的成功完成将进一步阐明我们对哺乳动物生殖功能中枢调节的理解，并为未来研究确定排卵前内分泌系统与行为融合的机制铺平道路。 预计该项目将为博士后、研究生、大学生和/或高中生提供科学培训。