A Neural Circuit Underlying the Generation of Hot Flushes

Cell Rep. 2018 Jul 10;24(2):271-277. doi: 10.1016/j.celrep.2018.06.037.


Hot flushes are a sudden feeling of warmth commonly associated with the decline of gonadal hormones at menopause. Neurons in the arcuate nucleus of the hypothalamus that express kisspeptin and neurokinin B (Kiss1ARH neurons) are candidates for mediating hot flushes because they are negatively regulated by sex hormones. We used a combination of genetic and viral technologies in mice to demonstrate that artificial activation of Kiss1ARH neurons evokes a heat-dissipation response resulting in vasodilation (flushing) and a corresponding reduction of core-body temperature in both females and males. This response is sensitized by ovariectomy. Brief activation of Kiss1ARH axon terminals in the preoptic area of the hypothalamus recapitulates this response, while pharmacological blockade of neurokinin B (NkB) receptors in the same brain region abolishes it. We conclude that transient activation of Kiss1ARH neurons following sex-hormone withdrawal contributes to the occurrence of hot flushes via NkB release in the rostral preoptic area.

Keywords: chemogenetics; estrogen; hot flashes; kisspeptin; menopause; neurokinin B; optogenetics; temperature regulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Axons / drug effects
  • Axons / metabolism
  • Estrogens / metabolism
  • Female
  • Hot Temperature
  • Kisspeptins / metabolism
  • Male
  • Mice
  • Neural Pathways / drug effects
  • Neural Pathways / physiology*
  • Neurokinin-1 Receptor Antagonists / pharmacology
  • Optogenetics
  • Preoptic Area / drug effects
  • Preoptic Area / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, Tachykinin / metabolism
  • Vasodilation* / drug effects


  • Estrogens
  • Kisspeptins
  • Neurokinin-1 Receptor Antagonists
  • Proto-Oncogene Proteins c-fos
  • Receptors, Tachykinin