Evidence that RF-amide related peptides are inhibitors of reproduction in mammals

Gonadotropin releasing hormone (GnRH) secretion represents the final common pathway in the control of the reproductive axis. Dogma has been that GnRH is solely responsible for the control of gonadotropin secretion, but emerging data presents a strong case for the existence of a gonadotropin inhibitory hormone in mammals. This evidence arose from initial work in avian species to isolate and identify a factor that inhibited gonadotropin release, which is known as gonadotropin inhibitory hormone (GnIH). The mammalian ortholog of avian GnIH is named RF-amide related peptide (RFRP). There are two forms of RFRP in mammals, RFRP-1 and RFRP-3 encoded by a single gene, but there has been skepticism and controversy as to whether these peptides play a significant role in the regulation of gonadotropin secretion. There is now a significant body of evidence that one or more RFRP exists in mammals and acts as an inhibitor of GnRH and/or gonadotropin secretion. Moreover, RFRP-producing neurons have been shown to transmit information to GnRH cells and/or gonadotropes in relation to seasonal status and to coordinate events around the preovulatory luteinizing hormone surge. This review will focus on the significant advances in RFRP research in mammalian species.