Regulation of LH secretion by RFRP-3-From the hypothalamus to the pituitary

RFamide-related peptides (RFRPs) have long been identified as inhibitors of the hypothalamus-pituitary-gonad axis in mammals. However, less progress has been made in the detailed roles of RFRPs in the control of LH secretion. Recent studies have suggested that RFRP-3 neurons in the hypothalamus can regulate the secretion of LH at different levels, including kisspeptin neurons, GnRH neurons, and the pituitary. Additionally, conflicting results regarding the effects of RFRP-3 on these levels exist. In this review, we collect the latest evidence related to the effects of RFRP-3 neurons in regulating LH secretion by acting on kisspeptin neurons, GnRH neurons, and the pituitary and discuss the potential role of the timely reduction of RFRP-3 signaling in the modulation of the preovulatory LH surge.