Ultrashortloop Feedback on GnRH Biosynthesis and Secretion

GnRH 生物合成和分泌的超短环反馈

• 批准号: 0544150
• 负责人: Tao-Yiao Wu
• 金额: $ 30.08万
• 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: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0544150&HistoricalAwards=false
• 关键词: Ultrashortloop; Feedback; GnRH; Biosynthesis; Secretion

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. Recently it has been discovered that the metabolite of GnRH, the pentapeptide, GnRH-(1-5), can directly regulate its gene expression as well as to facilitate reproductive behavior in the ovariectomized estrogen-primed rat. These results have led to the overarching hypothesis that this metabolite of GnRH, GnRH-(1-5) may be important for the synchronization of the preovulatory GnRH/LH surge with the initiation of reproductive behavior in the rodent. The studies in the current project will provide a fundamental understanding for how this metabolite of GnRH, GnRH-(1-5), is physiologically important for the regulation of pulsatile GnRH secretion. The experiments are designed to enhance our understanding of the cellular and molecular mechanisms underlying this processed metabolite's action in the brain. It is anticipated that this project will involve a graduate student, 1-2 rotating graduate student(s), and at least 5 college or high school students. The high school/college students will participate through summer programs or chapters of science/educational foundations as well as local undergraduate institutions. The high school/college projects will involve the central injections of peptides or inhibitors. The students will be involved in data presentation at weekly meetings as well as the publication process.

促性腺激素释放激素(GnRH)是哺乳动物生殖功能和行为的中枢调节因子。它从下丘脑分泌，诱导促性腺激素释放，进而刺激性腺功能。最近发现，GnRH的代谢产物GnRH-(1-5)可以直接调节其基因表达，促进去卵巢雌激素诱导的大鼠的生殖行为。这些结果导致了一个重要的假设，即GnRH的代谢物GnRH-(1-5)可能对啮齿类动物排卵前GnRH/LH峰与生殖行为的启动同步起重要作用。本项目的研究将为GnRH的代谢物GnRH-(1-5)如何在生理上调节脉动性GnRH分泌提供一个基本的理解。这些实验旨在加强我们对这种加工过的代谢物在大脑中作用的细胞和分子机制的理解。预计该项目将包括一名研究生，1-2名轮流研究生(S)，以及至少5名大学生或高中生。高中生/大学生将通过暑期项目或科学/教育基金会的分会以及当地的本科生机构参加。高中/大学的项目将涉及到中心注射多肽或抑制剂。学生们将参与每周会议上的数据演示以及发布过程。