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Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?

Fergani, C, Mazzella, L, Coolen, LM, McCosh, RB, Hardy, SL, Newcomb, N, Grachev, P, Lehman, MN and Goodman, RL (2016) Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes? Endocrinology, 157 (12). pp. 4829-1565. ISSN 0013-7227

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Abstract

There is now general agreement that neurokinin B (NKB) acts via neurokinin-3-receptor (NK3R) to stimulate secretion of GnRH and LH in several species, including rats, mice, sheep, and humans. However, the roles of two other tachykinins, substance P (SP) and neurokinin A, which act primarily via NK1R and NK2R, respectively, are less clear. In rodents, these signaling pathways can stimulate LH release and substitute for NKB signaling; in humans, SP is colocalized with kisspeptin and NKB in the mediobasal hypothalamus. In this study, we examined the possible role of these tachykinins in control of the reproductive axis in sheep. Immunohistochemistry was used to describe the expression of SP and NK1R in the ovine diencephalon and determine whether these proteins are colocalized in kisspeptin or GnRH neurons. SP-containing cell bodies were largely confined to the arcuate nucleus, but NK1R-immunoreactivity was more widespread. However, there was very low coexpression of SP or NK1R in kisspeptin cells and none in GnRH neurons. We next determined the minimal effective dose of these three tachykinins that would stimulate LH secretion when administered into the third ventricle of ovary-intact anestrous sheep. A much lower dose of NKB (0.2 nmol) than of neurokinin A (2 nmol) or SP (10 nmol) consistently stimulated LH secretion. Moreover, the relative potency of these three neuropeptides parallels the relative selectivity of NK3R. Based on these anatomical and pharmacological data, we conclude that NKB-NK3R signaling is the primary pathway for the control of GnRH secretion by tachykinins in ewes.

Item Type: Article
Additional Information: This is a pre-copyedited, author-produced version of an article accepted for publication in Endocrinology following peer review. The version of record Chrysanthi Fergani, Leanne Mazzella, Lique M. Coolen, Richard B. McCosh, Steven L. Hardy, Nora Newcomb, Pasha Grachev, Michael N. Lehman, Robert L. Goodman; Do Substance P and Neurokinin A Play Important Roles in the Control of LH Secretion in Ewes?, Endocrinology, Volume 157, Issue 12, 1 December 2016, Pages 4829–4841 is available online at: http://dx.doi.org/10.1210/en.2016-1565
Uncontrolled Keywords: 07 Agricultural And Veterinary Sciences, 11 Medical And Health Sciences, 06 Biological Sciences
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine
Divisions: Natural Sciences and Psychology
Publisher: Oxford University Press (OUP)
Related URLs:
Date Deposited: 26 Jun 2018 11:43
Last Modified: 26 Jun 2018 11:43
DOI or Identification number: 10.1210/en.2016-1565
URI: http://researchonline.ljmu.ac.uk/id/eprint/8792

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