GnIH Control of Feeding and Reproductive Behaviors

Abstract

In 2000, Tsutsui and colleagues discovered a neuropeptide gonadotropin-inhibitory hormone (GnIH) that inhibits gonadotropin release in birds. Subsequently, extensive studies during the last 15 years have demonstrated that GnIH is a key neurohormone that regulates reproduction in vertebrates, acting in the brain and on the pituitary to modulate reproduction and reproductive behavior. On the other hand, deprivation of food and other metabolic challenges inhibit the reproductive axis as well as sexual motivation. Interestingly, recent studies have further indicated that GnIH controls feeding behavior in vertebrates, such as in birds and mammals. This review summarizes the discovery of GnIH and its conservation in vertebrates and the neuroendocrine control of feeding behavior and reproductive behavior by GnIH.

Gonadotropin-Inhibitory Hormone Plays Roles in Stress-Induced Reproductive Dysfunction

“…Because the identified neuropeptides possess LPXRFamide (X = L or Q) motif at their C-termini, the mammalian GnIH orthologous gene and peptide are called Rfrp and RFRP-3, respectively. GnIH/RFRP-3 neurons project to the median eminence in birds and female sheep and suppress the secretion and synthesis of gonadotropin via GnIH/RFRP-3 receptor GPR147 under both in vivo and in vitro conditions in male birds, female rats, and female sheep (19, 22, 24, 25). GnIH/RFRP-3 neurons also project to GnRH neurons and inhibit their activity via GPR147 in birds and mammals (22, 26, 27).…”

“…Therefore, GnIH/RFRP-3 inhibits gonadotropin secretion and synthesis through direct and indirect actions on the pituitary. It has been shown that GnIH/RFRP-3 inhibits GnRH-elicited gonadotropin release and decreases LH pulse amplitude in female sheep (22, 24), and GnIH/RFRP-3 activity is decreased by high estradiol (E2) concentrations at the time of the GnRH/LH surge in female hamsters (Figure 1A) (20, 22). Similarly, elevated estrogen lowers Rfrp mRNA levels in male and female mice (28).…”

“…A breakthrough occurred in the early 21st century when a novel RFamide peptide that directly suppresses GnRH/gonadotropin synthesis and secretion was newly discovered (19). In birds, this neuropeptide was named gonadotropin-inhibitory hormone (GnIH), and later studies have shown that GnIH and its receptor, G-protein-coupled receptor (GPR) 147, have pivotal roles in the regulation of physiological function of the HPG axis, such as GnRH pulses and surges, in many species (20–22). The mammalian orthologous gene and peptide for avian GnIH are called Rfrp and RFRP-3, respectively.…”

The roles of kisspeptin and gonadotropin inhibitory hormone in stress-induced reproductive disorders

“…As this neuropeptide was the first hypothalamic factor that was found to suppress gonadotropin release, it was named GnIH based on its biological activity. GnIH molecules were subsequently identified in other vertebrates, mammals, primates, and humans [68][69][70]. The mammalian GnIH orthologous gene and peptide are named Rfrp and RFRP-3, respectively, because the neuropeptide possesses the LPXRFamide (X = L or Q) motif in its C-terminus.…”

“…Hypothalamic GnIH/ RFRP-3 neurons are mainly located in the paraventricular nucleus in birds and the dorsomedial hypothalamic area in mammals [71]. GnIH/RFRP-3 neurons project to the median eminence in birds and female sheep, and suppress the synthesis and secretion of gonadotropins at the pituitary level via the GnIH/RFRP-3 receptor GPR147 under both in vivo and in vitro conditions in male birds, female rats, and female sheep [17,26,69,72]. In addition, GnIH/RFRP-3 neurons project to GnRH neurons in the hypothalamus and suppress their activity via GPR147 in mammals and birds [23,26,73].…”