Kisspeptin Neurons from Mice to Men: Similarities and Differences

Abstract

The discovery that kisspeptin was critical for normal fertility in humans ushered in a new chapter in our understanding of the control of GnRH secretion. In this paper, we will review recent data on the similarities and differences across several mammalian species in the role of kisspeptin in reproductive neuroendocrinology. In all mammals examined to date, there is strong evidence that kisspeptin plays a key role in the onset of puberty and is necessary for both tonic and surge secretion of GnRH in adults, although kisspeptin-independent systems are also apparent in these studies. Similarly, two groups of kisspeptin neurons, one in the arcuate nucleus (ARC) and the other more rostrally, have been identified in all mammals, although the latter is concentrated in a limited area in rodents and more scattered in other species. Estrogen has divergent actions on kisspeptin expression in these two regions across these species, stimulating it the latter and inhibiting expression in the former. There is also strong evidence that the rostral population participates in the GnRH surge, whereas the ARC population contributes to steroid-negative feedback. There may be species differences in the role of these two populations in puberty, with the ARC cells important in rats, sheep, and monkeys, whereas both have been implicated in mice. ARC kisspeptin neurons also appear to participate in the GnRH surge in sheep and guinea pigs, whereas the data on this possibility in rodents are contradictory. Similarly, both populations are sexually dimorphic in sheep and humans, whereas most data in rodents indicate that this occurs only in the rostral population. The functional consequences of these species differences remain to be fully elucidated but are likely to have significance for understanding normal neuroendocrine control of reproduction as well as for use of kisspeptin agonists/antagonists as a therapeutic tool.

Sex differences in the physiology of eating

“…The recently discovered hypothalamic peptides kisspeptin (268,283,377,552) and gonadatropin-inhibitory peptide (GnIH) or RFamide-related peptide-3 (127,407,745) play important roles in HPG axis function. In mice and rats, kisspeptin is expressed most densely in the preoptic area, anteroventral periventricular nucleus (AVPV), and arcuate nucleus (the latter is often called the infundibular nucleus in humans).…”

Central Autonomic System

“…The arcuate nucleus and retrochiasmatic area contain many neurons that regulate endocrine, behavioral, and metabolic functions related to feeding and reproduction (Hökfelt et al, 1989;Goodman and Lehman, 2012;Liu et al, 2012). The arcuate neurons provide intense projections to other medial hypothalamic cells groups, including the paraventricular nucleus and periventricular preoptic area (Yeo and Herbison, 2011).…”

Leukemia Inhibitory Factor Represses GnRH Gene Expression via cFOS during Inflammation in Male Mice

“…LH and FSH act on the gonads to promote steroidogenesis and gametogenesis. GnRH neuronal processes, named “dendrons,” by Herbison group [3], form an interwoven network that receives direct synaptic and neuropeptide input from upstream regulatory neurons, most notably kisspeptin [4, 5]. This GnRH network integrates other signals that impinge on reproduction, such as stress [6, 7], endocrine disruptors [8], circadian rhythms [9, 10], metabolism [11, 12], and acute inflammation during infection [13-15].…”