Ultrashortloop Feedback on GnRH Biosynthesis and Secretion

Henry M Jackson Fdn For Advmt Of Military Medicine, Bethesda MD

Investigators

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. 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.