Contribution of GnIH Research to the Progress of Reproductive Neuroendocrinology

Abstract

Since the discovery of gonadotropin-releasing hormone (GnRH) in mammals at the beginning of the 1970s, it was generally accepted that GnRH is the only hypothalamic neuropeptide regulating gonadotropin release in mammals and other vertebrates. In 2000, however, gonadotropin-inhibitory hormone (GnIH), a novel hypothalamic neuropeptide that actively inhibits gonadotropin release, was discovered in quail. Numerous studies over the past decade and a half have demonstrated that GnIH serves as a key player regulating reproduction across vertebrates, acting on the brain and pituitary to modulate reproductive physiology and behavior. In the latter case, recent evidence indicates that GnIH can regulate reproductive behavior through changes in neurosteroid, such as neuroestrogen, biosynthesis in the brain. This review summarizes the discovery of GnIH, and the contributions to GnIH research focused on its mode of action, regulation of biosynthesis, and how these findings advance our understanding of reproductive neuroendocrinology.

GnIH Control of Feeding and Reproductive Behaviors

“…The identified mammalian GnIH peptides possess C-terminal LPXRFamide (X = L or Q) as a common motif, as in avian GnIH and GnIH-RPs [for reviews, see Ref. (16, 17, 21–25)] (Tables 1 and 2). GnIH peptides were named LPXRFamide peptides based on the structure of their C-terminal.…”

“…Accordingly, GnIH peptides are produced in the brains of vertebrates across fish to humans [see Ref. (14–25) for reviews]. Three GnIHs, gfLPXRFa-1, -2, and -3 are encoded in goldfish GnIH precursor cDNA (52) (Table 2).…”

“…Interestingly, recent studies have further indicated that GnIH controls feeding behavior in vertebrates, such as in mammals and birds [for reviews, see Ref. (25, 26)]. Thus, the last 15 years of GnIH research has contributed to a better understanding of the mechanism of neuroendocrine regulation of feeding and reproductive behaviors as well as reproduction [for reviews, see Ref.…”

RFamide-related peptide-3 (RFRP-3) suppresses sexual maturation in a eusocial mammal

“…RFamide-related peptide-3 [RFRP-3; mammalian ortholog to gonadotropin-inhibitory hormone (GnIH)] has emerged as an important component of the pathway of environmentally mediated reproductive inhibition (10), yet no evidence has linked the RFRP-3 system to onset or delay of puberty. In all vertebrates studied, a subset of GnRH neurons express RFRP-3's high-affinity receptor, GPR147 (11,12), and are apposed by RFRP-3 fibers originating in the dorsomedial nucleus of the hypothalamus (DMH) or paraventricular nucleus (PVN) (13)(14)(15).…”

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.…”