Abstract
Gonadotropin-inhibitory hormone (GnIH) was first discovered in the Japanese quail, and peptides with a C-terminal LPXRFamide sequence, the signature protein structure defining GnIH orthologs, are well conserved across vertebrate species, including fish, reptiles, amphibians, avians, and mammals. In the mammalian brain, three RFamide-related proteins (RFRP-1, RFRP-2, RFRP-3 = GnIH) have been identified as orthologs to the avian GnIH. GnIH is found primarily in the hypothalamus of all vertebrate species, while its receptors are distributed throughout the brain including the hypothalamus and the pituitary. The primary role of GnIH as an inhibitor of gonadotropin-releasing hormone (GnRH) and pituitary gonadotropin release is well conserved in mammalian and non-mammalian species. Circadian rhythmicity of GnIH, regulated by light and seasons, can influence reproductive activity, mating behavior, aggressive behavior, and feeding behavior. There is a potential link between circadian rhythms of GnIH, anxiety-like behavior, sleep, stress, and infertility. Therefore, in this review, we highlight the functions of GnIH in biological rhythms, social behaviors, and reproductive and non-reproductive activities across a variety of mammalian and non-mammalian vertebrate species.
Highlights
Pituitary gonadotropins, stimulated by gonadotropin-releasing hormone (GnRH), did not have any known inhibitory hormone until the discovery of a novel RFamide neuropeptide [RFamide-related protein (RFRP)] in birds [1]
gonadotropin-inhibitory hormone (GnIH) cell bodies are observed in high density in the dorsomedial nucleus of the hypothalamus (DMH), with their terminals projecting to the internal layer of the median eminence and to several midbrain regions including the diagonal band of Broca, preoptic area (POA), and the anterior pituitary [40]
G protein-coupled receptors (GPCRs) for GnIH were first identified by Hinuma et al [7] where they found a cDNA that encoded a GPCR that responded to RFRP-1 and RFRP-3
Summary
Pituitary gonadotropins, stimulated by gonadotropin-releasing hormone (GnRH), did not have any known inhibitory hormone until the discovery of a novel RFamide neuropeptide [RFamide-related protein (RFRP)] in birds [1]. In each of these peptides, a similar C-terminal LPXRFamide (X = L or Q) sequence is observed, indicating evolutionary conservation of the amino acid motif within mammalian and non-mammalian vertebrates [14] While this suggests that LPXRFamides share a common trait in regulating pituitary functions and inhibiting GnRH, they have diversified in their hypophysiotropic activities, in non-mammalian vertebrates [15]. In vitro hypothalamic GnIH neurons have been demonstrated to express glucocorticoid receptors [24], and Son et al [25] have identified glucocorticoid responsive elements in the promoter region of the rat npvf gene that are receptive to corticosterone as well as corticosterone-stimulated recruitment of glucocorticoid receptors These discoveries describe a molecular mechanism for the regulation of the GnIH system under stress that involves direct action by glucocorticoids. We highlight the functions of GnIH in reproductive rhythms, behaviors, and non-reproductive activities across a variety of mammalian and non-mammalian vertebrate species
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