The Effects of Kisspeptin on Gonadotropin Release in Non-human Mammals

Abstract

The Kiss1 gene encodes a 145-amino acid pre-peptide, kisspeptin, which is cleaved into smaller peptides of 54, 14, 13, and 10 amino acids. This chapter reviews in detail the effects of kisspeptin on gonadotropin secretion in non-human mammals. Studies of kisspeptin's effects have included both acute and chronic administration regimens via a number of administration routes. Acute kisspeptin stimulates gonadotropin secretion in a wide range of species of non-human mammals, including rats, mice, hamsters, sheep, pigs, goats, cows, horses, and monkeys. In general, the stimulatory effect of kisspeptin treatment is more pronounced for LH than FSH secretion. Kisspeptin is thought to exert its stimulatory effects on LH and FSH release via stimulation of GnRH release from the hypothalamus, since pre--administration of a GnRH antagonist prevents kisspeptin's stimulation of gonadotropin secretion. Although the kisspeptin receptor is also expressed on anterior pituitary cells of some species, and incubation of anterior pituitary cells with high concentrations of kisspeptin can stimulate in vitro LH release, the contribution of direct effects of kisspeptin on the pituitary is thought to be negligible in vivo. Continuous kisspeptin administration results in reduced sensitivity to the effects of kisspeptin, in some species. This desensitization is thought to occur at the level of the kisspeptin receptor, since the response of the pituitary gland to exogenous GnRH is maintained. Overall, the findings discussed in this chapter are invaluable to the understanding of the reproductive role of kisspeptin and the potential therapeutic uses of kisspeptin for the treatment of fertility disorders.

The Medio-Basal Hypothalamus as a Dynamic and Plastic Reproduction-Related Kisspeptin-gnrh-Pituitary Center in Fish

“…However, despite the fact that kisspeptin is found in the median eminence-hypophysial portal blood (21), and that kisspeptin and its receptor are expressed in the pituitary (19,22,23), this pathway is considered negligible in mammals (21,24). The presence of kisspeptin receptor in fish pituitary is also reported (10) as well as in vitro stimulatory effect on Lh and Gh secretion in the goldfish (18) or an inhibitory effect on Lh, as in the case of the European eel (23).…”

Defining Subpopulations of Arcuate Nucleus GABA Neurons in Male, Female, and Prenatally Androgenized Female Mice

“…Nevertheless, optogenetic studies have recently shown that target actions of ARN kisspeptin input are predominantly glutamatergic as opposed to GABAergic [39,40] . Kisspeptin is a potent and critical regulator of GnRH neurons [41] , and there is an ongoing hypothesis that the ARN kisspeptin population is involved in mediating gonadal steroid hormone negative feedback to GnRH neurons [42] . While there is no question that ARN kisspeptin neurons are involved in driving GnRH/LH release [43] , the present data suggest that ARN kisspeptin neurons are almost entirely distinct from the previously reported ARN GABA neurons that send dense, plastic projections to the GnRH neuron cell bodies [15] .…”

Potential Clinical Use of Kisspeptin

“…The nomenclature represents the number of amino acids: kisspeptin-54, -14, -13, and -10, and all lengths share the same C-terminal decapeptide sequence [3]. Kisspeptin-54 is the most abundant circulating isoform in humans, but both kisspeptin-10 and -54, when administered to humans and animals, have been shown to be potent stimulators of endogenous gonadotropin hormone secretion, albeit with slightly different pharmacokinetic properties [6,7,8,9,10,11]. Data from animal studies, however, shows that when pre-administered with a gonadotropin-releasing hormone (GnRH) antagonist, the stimulatory effect of kisspeptin is completely inhibited [12].…”