The RFamide-related peptides (RFRPs) are the group of neuropeptides synthesized predominantly from the hypothalamus that negatively affects the hypothalamo-hypophyseal-gonadal (hypothalamic–pituitary–gonadal [HPG]) axis. These peptides are first identified in quail brains and emerged as the mammalian orthologs of avian gonadotropin inhibitory hormones. The RFRP-3 neurons in the hypothalamus are present in several mammalian species. The action of RFRP-3 is mediated through a G-protein-coupled receptor called OT7T022. The predominant role of RFRP-3 is the inhibition of HPG axis with several other effects such as the regulation of metabolic activity, stress regulation, controlling of non-sexual motivated behavior, and sexual photoperiodicity in concert with other neuropeptides such as kisspeptin, neuropeptide-Y (NPY), pro-opiomelanocortin, orexin, and melanin. RFamide peptides synthesized in the granulosa cells, interstitial cells, and seminiferous tubule regulate steroidogenesis and gametogenesis in the gonads. The present review is intended to provide the recent findings that explore the role of RFRP-3 in regulating HPG axis and its potential applications in the synchronization of reproduction and its therapeutic interventions to prevent stress-induced amenorrhea.

Keywords: hypothalamic–pituitary–gonadal axis, reproduction, RFamide-related peptides-3.