This research project will extend the exciting finding from Dr. Rubin's laboratory, the recent discovery of a new form of gonadotropin releasing hormone (GnRH) in guinea pig (gp) brain. GnRH is the primary hypothalamic signal that regulates the pituitary-gonadal axis and is critical for reproductive success. Prior to this unexpected finding, mammalian (m) GnRH was presumed to be the neuroendocrine form of GnRH in all mammals. The newly identified form of GnRH includes a substitution in amino acid 2 which is conserved in all 11 known forms of GnRH and has been considered essential for binding to and activation of the GnRH receptor. The relative abilities of gpGnRH and mGnRH to stimulate gonadotropin release from guinea pig and rat pituitaries in vitro will be evaluated in Specific aim 1 and will provide important information regarding the biological activity of gpGnRH. A specific antibody to gpGnRH will be generated in Specific Aim 2 which will enable Dr. Rubin to determine the precise localization of this unique form of GnRH in guinea pig brain and the eventual evaluation of the presence of gpGnRH in other species. The data obtained in these studies will provide information about GnRH receptor-ligand interactions. This information will be used to direct future examination of a potential complementary change in the guinea pig receptor and/or mechanisms that might have evolved to compensate for a reduction in the biopotency of gpGnRH. These studies will enhance our understanding of the evolution of this essential hormone as well as the evolutionary lineage of the guinea pig.
