Elsevier

Peptides

Volume 32, Issue 9, September 2011, Pages 1972-1978
Peptides

Review
Tachykinins and the hypothalamo–pituitary–gonadal axis: An update

https://doi.org/10.1016/j.peptides.2011.07.009Get rights and content

Abstract

Tachykinins play a critical role in neuroendocrine regulation of reproduction. The best known members of the family are substance P (SP), neurokinin A and neurokinin B. Tachykinins mediate their biological actions through three G protein-coupled receptors, named NK1, NK2, and NK3. SP was suggested to play an important role in the ovulatory process in mammals and humans. Recent findings suggest a role of tachykinins in the aging of the hypothalamo–pituitary–gonadal axis. A high presence of SP was found in the sheep pars tuberalis and evidence indicates that it may have some role in the control of prolactin secretion. The presence of SP was confirmed in Leydig cells of the rat testes of animals submitted to constant light or treated with estrogens. Tachykinins were found to increase the motility of human spermatozoa. Tachykinins were also found to be present in the mouse ovary and more specifically, in the granulose cells. It is possible that tachykinins may play an important role in the ovarian function. NKB has been implicated in the steroid feedback control of GnRH release. Human mutations in the gene encoding this peptide or its receptor (TACR3) lead to a defect in the control of GnRH. A specific subset of neurons in the arcuate nucleus of the hypothalamus, colocalized three neuropeptides, kisspeptin, NKB and dynorphin. This subpopulation of neurons mediates the gonadal hormone feedback control of GnRH secretion. NKB/NK3 signaling plays a role in puberty onset and fertility in humans. This minireview summarizes the recent data about the action of tachykinins on the hypothalamo–pituitary–gonadal axis.

Highlights

► Substance P and Neurokinin B play a role in neuroendocrine control of reproduction. ► Strong evidence indicates that arcuate NKB/dynorphin/kisspeptin neurons regulate pulsatile secretion of GnRH. ► A better understanding of the mechanisms involved in the arcuate NK3 receptor signaling could contribute to improve treatment of reproductive disorders.

Section snippets

Studies on primates and humans

Plasma levels of SP were studied during the menstrual cycle in monkeys and humans [43], [44]. In the cynomolgus monkey it was observed that plasma SP levels showed significant variations during the menstrual cycle, with higher levels in the follicular phase than in the following luteal period. During the follicular phase there was a negative correlation between plasma levels of estradiol and SP. These results indicate that SP may have a significant role in the events that result in the

Neurokinin B

In the past decade remarkable progress has been made regarding NKB and its role on the reproductive functions. Different methodologies have greatly contributed to our understanding of the role of this tachykinin on the hypothalamo–pituitary–gonadal axis. It has become evident that NKB fulfills a very critical role on this axis, and its main actions seem to be exerted at the hypothalamic level. Laboratory animals, receptor biology, human subjects, and molecular biology studies have all

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