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：脱氧肽促性激素释放激素（GNRH）是哺乳动物生殖功能和行为的核心调节剂。 从下丘脑分泌，诱导促性腺激素的释放，进而刺激促性腺功能。 GNRH释放的排卵前激增与性接受时期一致，最终导致排卵诱导。 初步结果表明，GnRH的代谢产物可能调节其生物合成以及诱导大鼠的性行为。 这些结果导致了过度的假设，即GNRH对于将GNRH激增与性行为的启动同步至关重要。 该建议将通过确定代谢物对GnRH生物合成的调节的基础机制来解决该假设的一个方面。 提出了三个具体目的，以确定（1）使用GT1-7细胞系作为体外模型发挥生物学作用所需的GNRH代谢产物； （2）GnRH代谢产物（S）参与大鼠（体内）调节GnRH基因表达的参与； （3）GnRH代谢产物调节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确定活性GNRH代谢产物，并确定代谢产物可以调节GnRH基因表达的机制。 这是第一个赋予GnRH代谢产物对GnRH基因表达的直接生物学作用的研究。 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的核心调节的理解，并将为未来的研究铺平道路，以确定内分泌系统在卵巢期期间与行为的融合的基础机制。 预计该项目将为博士后研究员，研究生以及大学和/或高中生提供科学培训。