Gonadotropin-Inhibitory Hormone Is a Hypothalamic Peptide That Provides a Molecular Switch between Reproduction and Feeding

Abstract

Objective: Gonadotropin-inhibitory hormone (GnIH)-3 is a neuropeptide that plays a major role in the regulation of reproduction and feeding in mammals. Materials and Methods: We measured endocrine and behavioural parameters of reproduction in sheep, and sexual behaviour in sheep, mice and cynomolgus monkeys. In addition, GnIH gene expression (in situ hybridization) was examined in ewes, and effects of GnIH-3 on food intake and energy expenditure were measured in various species. GnIH-3 was infused (i.v.) into ewes after an i.m. injection of estradiol benzoate to determine whether the peptide blocks the surge in luteinizing hormone (LH) secretion. Results: GnIH gene expression was reduced in the preovulatory period in ewes. Infusion (i.v.) of GnIH-3 blocked the estrogen-induced LH surge (in ewes). Intracerebroventricular infusion had no effect on female or male sexual behaviour in each of the three species, but increased food intake. There were no effects on energy expenditure in sheep or rats. GnIH increased fos protein (immunohistochemistry) was seen in orexigenic neurons (in sheep and rats), but also in anorexigenic neurons (in sheep). Conclusions: GnIH-3 reduces reproductive hormone levels and increases food intake in mammals without reducing energy expenditure. There is minimal effect on reproductive behaviour. The dual effect on reproduction and feeding suggests that GnIH-3 provides a molecular switch between these two functions. Blockade of the positive feedback effect of estrogen with parenteral infusion indicates that this peptide may have utility as a blocker of reproductive function in mammals.

Kisspeptin antagonist prevents RF9-induced reproductive changes in female rats

“…We provide in this study the first demonstration that RF9 has a strong food intake-suppressing effect in female rats with as low as 1 nmol. Our finding is indirectly in keeping with the data that GnIH-3 (RFRP-3) increases food intake in mammals without reducing energy expenditure (Clarke et al 2012). …”

“…Therefore, the effect of kisspeptin on food intake seems to weaken in older age. In keeping with our finding, there was no effect of kisspeptin on food intake in sheep (Clarke et al 2012). While central kisspeptin administration has been initially reported not to have any significant effects on food intake and body weight in rats (Castellano et al 2005), central administration of kisspeptin has been recently shown to increase meal intervals, resulting in a decrease in nocturnal food intake in mice (Stengel et al 2011).…”

SALMFamide salmagundi: The biology of a neuropeptide family in echinoderms

“…and it has been proposed that GnIH functions as a "molecular switch" between reproduction and 847 feeding in vertebrates [10] This review has looked back over a period of twenty-five years of research on 860…”

The involvement of gonadotropin inhibitory hormone and kisspeptin in the metabolic regulation of reproduction

“…Diverse data from a wide variety of vertebrate taxa indicate that these neuropeptides play a role in the regulation of reproduction in response to short-term (circadian) and long-term (seasonal) environmental changes , Clarke & Parkington 2014. Moreover, both neuropeptides act as conduits/mediators for transferring the impact of body internal cues such as gonadal steroids and current energy status to the reproductive axis (Smith et al 2007, Clarke et al 2012, Smith 2013.…”