Reproductive neuroendocrinology of mammalian gonadotropin‐inhibitory hormone

Abstract

Background Gonadotropin‐inhibitory hormone (GnIH) was discovered in the Japanese quail brain in 2000 as a hypothalamic neuropeptide that suppresses luteinizing hormone release from cultured quail anterior pituitary. Methods The authors investigated the existence of mammalian orthologous peptides to GnIH and their physiological functions in the following 19 years of research. Main findings Mammals have orthologous peptide to GnIH, often described RFamide‐related peptide, expressed in the hypothalamus and gonads. Mammalian GnIH may also suppress gonadotropin synthesis and release by suppressing gonadotropin‐releasing hormone (GnRH) synthesis and release in addition to directly suppressing gonadotropin synthesis and release from the pituitary. Mammalian GnIH may also suppress kisspeptin, a stimulator of GnRH, release. Mammalian GnIH is also expressed in the testis and ovary and suppresses gametogenesis and sex steroid production acting in an autocrine/paracrine manner. Thus, mammalian GnIH may act at all levels of the hypothalamic‐pituitary‐gonadal axis to suppress reproduction. GnIH may be involved in the regulation of puberty, estrous or menstrual cycle, seasonal reproduction, and stress responses. Conclusion Studies suggest that mammalian GnIH is an important neuroendocrine suppressor of reproduction in mammals.

Possible Role of GnIH as a Novel Link between Hyperphagia-Induced Obesity-Related Metabolic Derangements and Hypogonadism in Male Mice

“…Universally throughout the animal kingdom, energy deficits inhibit the reproductive axis, which demonstrates that reproduction is acutely sensitive to fuel availability. GnIH is well known for its crucial role in the regulation of the reproductive axis [ 12 , 18 , 19 , 20 ], but in light of accumulating data, it has emerged as a novel orexigenic neuropeptide that affects feeding and is potentially involved in energy metabolism [ 14 , 16 , 21 , 22 ]. However, the relationship between GnIH in reproduction and energy metabolism has not been studied.…”

Modeling circadian regulation of ovulation timing: age-related disruption of estrous cyclicity

“…Except for late afternoon of proestrus at which the LH surge occurs, plasma LH levels are very low throughout estrous cycles 58 . This is at least partly because of negative feedback effect of estrogen on gonadotroph 59 and the effect of gonadotropin-inhibitory hormone (GnIH) decreasing the activity of GnRH neurons 60 . Although several factors including increase of GnRH receptors in the pituitary 61 and positive effect of estradiol on gonadotroph 59 have been implicated in the occurrence of the LH surge, the surge release of GnRH seems to be indispensable to the LH surge 53 , 62 .…”

Signatures of adaptive evolution in platyrrhine primate genomes

“…Among the most notable genes recovered for capuchins is NPVF, found in both the ancestral Cebinae and across-capuchins branches, encoding the neuropeptides NPSF and NPVF (also referred to as the RFamide-related peptides, RFRP-1 and RFRP-3), which are mammalian homologs of the avian neuropeptide gonadotropin-inhibitory hormone. These neuropeptides act as potent negative regulators of gonadotropin synthesis and secretion, with a range of functions in the modulation of reproduction including the regulation of sexual behaviour, sexual maturation, ovulatory cycle, gonadal function, reproductive seasonality, and stress-induced reproductive suppression, among others (70).…”