description): This proposal is requesting funds for a very promising and exciting new direction of research that may shed light on a controversial issue in the scientific community. The proposes to isolate and characterize a novel form of gonadotropin-releasing hormone (GnRH), that is lamprey-like, in the primate hypothalamus. She proposes to test the hypothesis that the primate brain has two hypothalamic GnRHs. This hypothesis is based on recent data from preliminary and collaborative studies that support her earlier claims of a novel ir-GnRI-I (lamprey GnRH-like) form in humans. The applicant proposes to isolate and characterize this novel form of GnRH in the hypothalamus of primates by screening the cDNA libraries to hypothalamus using oligonucleotide probes against lamprey GnRH as well as other related probes. She theorizes that an ancient form of GnRH (lamprey) as well as the more modem mammalian form of GnRH function as hypothalamic neurohormones stimulating gonadotropin release in the primate. In mammals, it has not been fully explained how one GnRH hormone differentially stimulates the release of two gonadotropins (FSH and LH). She is in a unique position to accomplish this proposed project because she has recently identified a full length cDNA encoding the lamprey GnRH-I and has an established collaboration with research in humans. The presence of multiple GnRHs in the hypothalamus could provide the answer to this question.
Her specific aims i nclude 1) screening and isolating cDNA clones encoding the precursor forms of brain GnRH(S) in primates and (2) screening genomic libraries using the newly identified cDNAs as probes to isolate the complete GnRH gene(s). She predicts that findings from these studies will contribute to our understanding of reproductive physiology and provide further information for developing medical therapies using GnRH analogs. A new hypothalamic GnRH in mammals could shed light on the formation of new GnRH analogs that may not have some of the side effects noted with the GnRH analogs currently used.
| Bentley, George E; Moore, Ignacio T; Sower, Stacia A et al. (2004) Evidence for a novel gonadotropin-releasing hormone in hypothalamic and forebrain areas in songbirds. Brain Behav Evol 63:34-46 |
