The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction

Víctor M. Navarro, Martha A. Bosch, Silvia León, Serap Simavli, Cadence True, Leonor Pinilla, Rona S. Carroll, Stephanie B. Seminara, Manuel Tena-Sempere, Oline Ronnekleiv, Ursula B. Kaiser

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r-/- mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreasedLHrelease in ovariectomized-sham replaced females, as documented forNK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100% Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons andGnRHneurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.

Original languageEnglish (US)
Pages (from-to)627-637
Number of pages11
JournalEndocrinology
Volume156
Issue number2
DOIs
StatePublished - Feb 1 2015

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Kisspeptins
Neurokinin A
Tachykinins
Neurokinin B
Reproduction
Substance P
Arcuate Nucleus of Hypothalamus
Neurokinin-1 Receptors
Gonadotropins
Neurons
Gonadotropin-Releasing Hormone
Estradiol
Messenger RNA

ASJC Scopus subject areas

  • Endocrinology

Cite this

Navarro, V. M., Bosch, M. A., León, S., Simavli, S., True, C., Pinilla, L., ... Kaiser, U. B. (2015). The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. Endocrinology, 156(2), 627-637. https://doi.org/10.1210/en.2014-1651

The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. / Navarro, Víctor M.; Bosch, Martha A.; León, Silvia; Simavli, Serap; True, Cadence; Pinilla, Leonor; Carroll, Rona S.; Seminara, Stephanie B.; Tena-Sempere, Manuel; Ronnekleiv, Oline; Kaiser, Ursula B.

In: Endocrinology, Vol. 156, No. 2, 01.02.2015, p. 627-637.

Research output: Contribution to journalArticle

Navarro, VM, Bosch, MA, León, S, Simavli, S, True, C, Pinilla, L, Carroll, RS, Seminara, SB, Tena-Sempere, M, Ronnekleiv, O & Kaiser, UB 2015, 'The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction', Endocrinology, vol. 156, no. 2, pp. 627-637. https://doi.org/10.1210/en.2014-1651
Navarro VM, Bosch MA, León S, Simavli S, True C, Pinilla L et al. The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. Endocrinology. 2015 Feb 1;156(2):627-637. https://doi.org/10.1210/en.2014-1651
Navarro, Víctor M. ; Bosch, Martha A. ; León, Silvia ; Simavli, Serap ; True, Cadence ; Pinilla, Leonor ; Carroll, Rona S. ; Seminara, Stephanie B. ; Tena-Sempere, Manuel ; Ronnekleiv, Oline ; Kaiser, Ursula B. / The integrated hypothalamic tachykinin-kisspeptin system as a central coordinator for reproduction. In: Endocrinology. 2015 ; Vol. 156, No. 2. pp. 627-637.
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abstract = "Tachykinins are comprised of the family of related peptides, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB). NKB has emerged as regulator of kisspeptin release in the arcuate nucleus (ARC), whereas the roles of SP and NKA in reproduction remain unknown. This work explores the roles of SP and NKA in the central regulation of GnRH release. First, central infusion of specific agonists for the receptors of SP (neurokinin receptor 1, NK1R), NKA (NK2R) and NKB (NK3R) each induced gonadotropin release in adult male and ovariectomized, estradiol-replaced female mice, which was absent in Kiss1r-/- mice, indicating a kisspeptin-dependent action. The NK2R agonist, however, decreasedLHrelease in ovariectomized-sham replaced females, as documented forNK3R agonists but in contrast to the NK1R agonist, which further increased LH release. Second, Tac1 (encoding SP and NKA) expression in the ARC and ventromedial nucleus was inhibited by circulating estradiol but did not colocalize with Kiss1 mRNA. Third, about half of isolated ARC Kiss1 neurons expressed Tacr1 (NK1R) and 100{\%} Tacr3 (NK3R); for anteroventral-periventricular Kiss1 neurons andGnRHneurons, approximately one-fourth expressed Tacr1 and one-tenth Tacr3; Tacr2 (NK2R) expression was absent in all cases. Overall, these results identify a potent regulation of gonadotropin release by the SP/NK1R and NKA/NK2R systems in the presence of kisspeptin-Kiss1r signaling, indicating that they may, along with NKB/NK3R, control GnRH release, at least in part through actions on Kiss1 neurons.",
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AU - Pinilla, Leonor

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