Neuropeptide control of gonadotropin secretion at the level of the anterior pituitary gland is primarily through the stimulatory action of the hypothalamic decapeptide, gonadotropin-releasing hormone (GnRH), which was originally isolated from mammals and subsequently from non-mammals including birds. Although studies of the different forms of GnRH and its receptors have revealed a wealth of information as to their function, an inhibitory hypothalamic neuropeptide for gonadotropin release has, until recently, remained unknown in any vertebrate. In 2000, a novel RFamide neuropeptide was found specifically to inhibit gonadotropin release in quail (Tsutsui et al., 2000). This peptide has now been named gonadotropin-inhibitory hormone (GnIH). A gonadotropin inhibitory system is an intriguing concept and provides an unprecedented opportunity to study the regulation of reproduction from an entirely novel standpoint. Recent findings in the PI's laboratory indicate that in addition to synthesis in the brain, GnIH is also synthesized in male and female gonads of songbirds. In addition, the receptor for GnIH is expressed in the gonads of both sexes. Expression of both GnIH and its receptor in the gonads provides the framework for an additional level of control of the reproductive system in response to environmental cues. Thus, it would be beneficial to the field of vertebrate reproductive biology in general to understand why GnIH and its receptor are expressed in the gonads. At present, almost nothing is known about this hormone system in the gonads. This project focuses on GnIH and its receptor in avian gonads in order to provide solid baseline data for further studies on the interactions of the hypothalamo-pituitary-gonadal axis. Without fundamental data on gonadal GnIH, its location and function, interpretations about brain-gonad interactions cannot be made correctly. The broader impacts of this research include training of graduate students in laboratories in different countries, undergraduate participation in research and scientific meetings, and inclusion of deserving undergraduates as authors on publications. Furthermore, the intellectual merit of the results obtained includes advancement our understanding of a novel hormone system which influences reproduction in all vertebrates studied to date. A great deal is known about GnIH in the brain, but how neural GnIH interacts with gonadal GnIH to time reproductive effort is unknown. This project will provide solid data upon which a deeper understanding of this newly-identified hormone system can be built.