Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons: A novel hypothesis on the mechanism of hot flushes

Naomi E. Rance, Penny A. Dacks, Melinda A. Mittelman-Smith, Andrej A. Romanovsky, Sally J. Krajewski-Hall

Research output: Contribution to journalReview article

106 Scopus citations

Abstract

Despite affecting millions of individuals, the etiology of hot flushes remains unknown. Here we review the physiology of hot flushes, CNS pathways regulating heat-dissipation effectors, and effects of estrogen on thermoregulation in animal models. Based on the marked changes in hypothalamic kisspeptin, neurokinin B and dynorphin (KNDy) neurons in postmenopausal women, we hypothesize that KNDy neurons play a role in the mechanism of flushes. In the rat, KNDy neurons project to preoptic thermoregulatory areas that express the neurokinin 3 receptor (NK3R), the primary receptor for NKB. Furthermore, activation of NK3R in the median preoptic nucleus, part of the heat-defense pathway, reduces body temperature. Finally, ablation of KNDy neurons reduces cutaneous vasodilatation and partially blocks the effects of estrogen on thermoregulation. These data suggest that arcuate KNDy neurons relay estrogen signals to preoptic structures regulating heat-dissipation effectors, supporting the hypothesis that KNDy neurons participate in the generation of flushes.

Original languageEnglish (US)
Pages (from-to)211-227
Number of pages17
JournalFrontiers in Neuroendocrinology
Volume34
Issue number3
DOIs
StatePublished - Aug 1 2013

Keywords

  • Estrogen
  • GnRH
  • LH
  • Menopause
  • Reproduction
  • Thermoregulation

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems

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