Studies Towards Understanding the Functional Significance of Multiple GnRHs in Vertebrate Brains

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PI: Zohar, Y. IBN-9723643 Gonadotropin releasing hormones (GnRH's) are decapeptides produced in the brain that are integral for reproduction in all vertebrates. These neurohormones function by regulating gonadotropin synthesis and release in the pituitary. The discovery, however, that in all vertebrates, multiple forms of GnRH coexist in the brain of a single species, indicates that during evolution GnRH's may have acquired additional functions that are not related to reproduction. The differential roles of the multiple GnRH's are not yet fully understood, and their relative involvement in reproduction has yet to be defined. Nine distinct forms of GnRH have been described thus far in vertebrates, out of which six are fish-specific. Although two to three forms of GnRH are now believed to be present in the brains of all vertebrates, perciform fish were the first, and to date, the only vertebrates in which three forms have been definitively identified in the brain of a single species. These three GnRH forms have been completely characterized both at the peptide and nucleotide level. Therefore, at present, perciform fish represent the best available model for studying the reproduction-related significance of GnRH multiplicity in vertebrates. The primary objective of the proposed research is to understand which of the multiple forms of GnRH are involved in the control of reproduction, and to elucidate the relative reproduction-related roles of these forms. The PI will use striped bass and gilthead seabream, both perciform fish possessing three GnRH forms as experimental models. The reproductive endocrinology of these fish has been studied extensively, and all biochemical and genetic tools required for the proposed studies are readily available. Three hypotheses will be tested: 1) That gene expression and peptide levels of those GnRH's that are involved in the regulation of reproduction vary at different stages of gonadal development; 2) That the gene expression an peptide levels of those forms that are involved in reproduction are responsive to environmental changes that influence gametogenesis; and, 3) That gene expression and peptide levels of reproductively-relevant GnRH's are regulated by gonadal steroid feedback. The results of these studies will contribute to the global understanding of the functional significance of GnRH multiplicity in all vertebrates including mammals. It is also expected that this research will pave the way for future studies concerned with the regulation of biosynthesis and release of GnRH forms relevant to reproduction , at the organisimal, cellular and molecular levels. Finally, as reproductive failure in farmed fish appears to be due to GnRH disruption, the results of this research may have significant implications for commercial fish farming.