Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse

Víctor M. Navarro, M. L. Gottsch, M. Wu, D. García-Galiano, S. J. Hobbs, M. A. Bosch, L. Pinilla, D. K. Clifton, A. Dearth, O. K. Ronnekleiv, R. E. Braun, R. D. Palmiter, M. Tena-Sempere, M. Alreja, R. A. Steiner

Research output: Contribution to journalArticle

166 Scopus citations

Abstract

Kisspeptin (Kiss1) and neurokinin B (NKB) (encoded by the Kiss1 and Tac2 genes, respectively) are indispensable for reproduction. In the female of many species, Kiss1 neurons in the arcuate nucleus (ARC) coexpress dynorphin A and NKB. Such cells have been termed Kiss1/NKB/Dynorphin (KNDy) neurons, which are thought to mediate the negative feedback regulation of GnRH/LH secretion by 17β-estradiol. However, we have less knowledge about the molecular physiology and regulation of Kiss1/Kiss1-expressing neurons in the ARC of the male. Our work focused on the adult male mouse, where we sought evidence for coexpression of these neuropeptides in cells in the ARC, assessed the role of Kiss1 neurons in negative feedback regulation of GnRH/LH secretion by testosterone (T), and investigated the action of NKB on KNDy and GnRH neurons. Results showed that 1) the mRNA encoding Kiss1, NKB, and dynorphin are coexpressed in neurons located in the ARC; 2) Kiss1 and dynorphin A mRNA are regulated by T through estrogen and androgen receptordependent pathways; 3) senktide, an agonist for theNKBreceptor (neurokinin 3 receptor, encoded by Tacr3), stimulates gonadotropin secretion; 4) KNDy neurons express Tacr3, whereas GnRH neurons do not; and 5) senktide activates KNDy neurons but has no discernable effect on GnRH neurons. These observations corroborate the putative role for KNDy neurons in mediating the negative feedback effects of T on GnRH/LH secretion and provide evidence that NKB released from KNDy neurons is part of an auto-feedback loop that generates the pulsatile secretion of Kiss1 and GnRH in the male.

Original languageEnglish (US)
Pages (from-to)4265-4275
Number of pages11
JournalEndocrinology
Volume152
Issue number11
DOIs
StatePublished - Nov 2011

ASJC Scopus subject areas

  • Endocrinology

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    Navarro, V. M., Gottsch, M. L., Wu, M., García-Galiano, D., Hobbs, S. J., Bosch, M. A., Pinilla, L., Clifton, D. K., Dearth, A., Ronnekleiv, O. K., Braun, R. E., Palmiter, R. D., Tena-Sempere, M., Alreja, M., & Steiner, R. A. (2011). Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology, 152(11), 4265-4275. https://doi.org/10.1210/en.2011-1143