Abstract
Gonadotropin-inhibitory hormone (GnIH) is a novel hypothalamic neuropeptide that was discovered in quail as an inhibitory factor for gonadotropin release. GnIH inhibits gonadotropin synthesis and release in birds through actions on gonadotropin-releasing hormone (GnRH) neurons and gonadotropes, mediated via the GnIH receptor (GnIH-R), GPR147. Subsequently, GnIH was identified in mammals and other vertebrates. As in birds, mammalian GnIH inhibits gonadotropin secretion, indicating a conserved role for this neuropeptide in the control of the hypothalamic-pituitary-gonadal (HPG) axis across species. Identification of the regulatory mechanisms governing GnIH expression and release is important in understanding the physiological role of the GnIH system. A nocturnal hormone, melatonin, appears to act directly on GnIH neurons through its receptor to induce expression and release of GnIH in quail, a photoperiodic bird. Recently, a similar, but opposite, action of melatonin on the inhibition of expression of mammalian GnIH was shown in hamsters and sheep, photoperiodic mammals. These results in photoperiodic animals demonstrate that GnIH expression is photoperiodically modulated via a melatonin-dependent process. Recent findings indicate that GnIH may be a mediator of stress-induced reproductive disruption in birds and mammals, pointing to a broad role for this neuropeptide in assessing physiological state and modifying reproductive effort accordingly. This paper summarizes the advances made in our knowledge regarding the regulation of GnIH synthesis and release in photoperiodic birds and mammals. This paper also discusses the neuroendocrine integration of environmental signals, such as photoperiods and stress, and internal signals, such as GnIH, melatonin, and glucocorticoids, to control avian and mammalian reproduction.
Highlights
The neuroendocrine integration of environmental and internal signals controls reproduction across vertebrate species
It was shown that melatonin directly induces gonadotropin-inhibitory hormone (GnIH) mRNA expression in the rat GnIH cell line (Gingerich et al, 2009). These results demonstrate that the expression of GnIH is photoperiodically modulated via a melatonin-dependent process in mammals, like in birds, how it is related to seasonal reproduction is not yet clear (Figure 1)
Birds that outcompeted others for nest boxes (“winners”) had significantly fewer numbers of GnIH-producing cells than those without nest boxes (“losers”) at the beginning of the breeding season (Calisi et al, 2011). This relationship changed with breeding stage; once “winners” had begun to incubate eggs, their GnIH content increased significantly above that of “losers.” whereas birds appeared reproductively capable across treatments, these findings indicate that hypothalamic GnIH may serve as a short-term modulator of reproductive behaviors in response to social environment
Summary
The neuroendocrine integration of environmental and internal signals controls reproduction across vertebrate species. Findings from the last 12 years, indicate that GnRH is not the sole hypothalamic regulatory neuropeptide of vertebrate reproduction, with gonadotropin-inhibitory hormone (GnIH) playing a key role in the inhibition of reproduction. In a search for novel neuropeptides regulating the release of pituitary hormones, Tsutsui and colleagues identified a novel hypothalamic neuropeptide that directly acts on the pituitary to inhibit gonadotropin release in quail and termed it GnIH (Tsutsui et al, 2000). This was the first demonstration of a hypothalamic neuropeptide inhibiting gonadotropin release in any vertebrate. From the past 12 years of research, we know that GnIH exists in a variety of avian species and regulates avian reproduction by decreasing gonadotropin release and synthesis via action on the anterior pituitary gland and the GnRH system, mediated via the www.frontiersin.org
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