Gonadotropin Inhibitory Hormone and Its Receptor: Potential Key to the Integration and Coordination of Metabolic Status and Reproduction

Abstract

Since its discovery as a novel gonadotropin inhibitory peptide in 2000, the central and peripheral roles played by gonadotropin-inhibiting hormone (GnIH) have been significantly expanded. This is highlighted by the wide distribution of its receptor (GnIH-R) within the brain and throughout multiple peripheral organs and tissues. Furthermore, as GnIH is part of the wider RF-amide peptides family, many orthologues have been characterized across vertebrate species, and due to the promiscuity between ligands and receptors within this family, confusion over the nomenclature and function has arisen. In this review, we intend to first clarify the nomenclature, prevalence, and distribution of the GnIH-Rs, and by reviewing specific localization and ligand availability, we propose an integrative role for GnIH in the coordination of reproductive and metabolic processes. Specifically, we propose that GnIH participates in the central regulation of feed intake while modulating the impact of thyroid hormones and the stress axis to allow active reproduction to proceed depending on the availability of resources. Furthermore, beyond the central nervous system, we also propose a peripheral role for GnIH in the control of glucose and lipid metabolism at the level of the liver, pancreas, and adipose tissue. Taken together, evidence from the literature strongly suggests that, in fact, the inhibitory effect of GnIH on the reproductive axis is based on the integration of environmental cues and internal metabolic status.

Genetic Basis of Sexual Maturation Heterosis: Insights From Ovary lncRNA and mRNA Repertoire in Chicken

“…Upon light stimulation, decreasing levels of MT results in a decrease in GnIH synthesis ( 69 ), thus alleviating the inhibition on the HPG axis and allowing for the release of GnRH and subsequent activation of gonad development ( 70 ). Consistent with the previous study ( 71 ), we found that chickens with earlier AFE and larger pubic space had higher GnRH content but lower MT content, suggesting that chickens with higher GnRH could give impetus to development of reproductive tissue, contributing to the sexual maturation in crossbreeds. Interestingly, the crossbreeds shared same photoperiod stimulus with purebreds, but exhibited significant heterosis for sexual maturation.…”

The possibly role of GnIH in stress and gut dysfunction in chicken

“…The results of GPR147 expression experiments in hens agreed with those of our and other previous studies, which demonstrated that the GnIH receptor is expressed in the colon, stomach, and ileum of mice, the intestine of piglets, and the posterior intestine of ratthe tilapia ( Li et al, 2012 ; Muñoz-Cueto et al, 2017 ; Gospodarska et al, 2019 ). In addition to GPR147, GnIH is expressed in the intestine, stomach, and multiple peripheral organs and tissues of several vertebrates ( Wang et al, 2018 ; Bédécarrats et al, 2022 ). These findings suggest that GnIH acts directly on the intestine via its receptor, GPR147, through autocrine and paracrine manner exerting physiological or pharmacological function secretion.…”

Continuous exposure to red light induces photorefractoriness in broiler breeder pullets

“…Thus, we hypothesize that the constant exposure to a long (red) wavelength, which is known to penetrate the skull more easily to stimulate the HPG axis ( Benoit, 1964 ; Menaker and Underwood, 1976 ; Mobarkey et al, 2010 ), resulted in the desensitization of deep brain photoreceptors. This would effectively impair the activation of the HPG axis, rendering the photoreceptors unable to respond to stimulatory photoperiods or wavelengths, despite the removal of inhibition via GnIH that has been linked to metabolic thresholds ( Bédécarrats et al, 2022 ). Alternatively, it is possible that red light results in an overproduction of GnRH, thus desensitizing its receptor on the anterior pituitary gland.…”

“…In fact, Ferreira et al (2019) demonstrated that broiler breeders remaining under non-stimulatory photoperiods of 8 or 10 h of light will still enter lay at ∼27 woa. This is likely due to the influence of body weight and metabolic factors, which also control the expression of GnIH ( Bédécarrats et al, 2022 ). Thus, it is possible that hens under sRED lighting overcame the desensitization of the photoreceptors.…”