TY - JOUR
T1 - Modulation of body temperature and LH secretion by hypothalamic KNDy (kisspeptin, neurokinin B and dynorphin) neurons
T2 - A novel hypothesis on the mechanism of hot flushes
AU - Rance, Naomi E.
AU - Dacks, Penny A.
AU - Mittelman-Smith, Melinda A.
AU - Romanovsky, Andrej A.
AU - Krajewski-Hall, Sally J.
N1 - Funding Information:
The work of the authors on hot flushes was supported by the National Institutes of Health (NIH) National Institute on Aging Grant R01 AG032315 (NER). We have also reviewed studies on thermoregulation that were supported by the NIH National Institute of Neurological Disorders and Stroke Grant R01 NS41233 (AAR). The authors are grateful for the expert advice and continuing support of Dr. Nathaniel T. McMullen. We would also like to acknowledge the Graduate Interdisciplinary Programs in Neuroscience and Physiology at the University of Arizona.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
KW - Estrogen
KW - GnRH
KW - LH
KW - Menopause
KW - Reproduction
KW - Thermoregulation
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U2 - 10.1016/j.yfrne.2013.07.003
DO - 10.1016/j.yfrne.2013.07.003
M3 - Review article
C2 - 23872331
AN - SCOPUS:84881317899
SN - 0091-3022
VL - 34
SP - 211
EP - 227
JO - Frontiers in Neuroendocrinology
JF - Frontiers in Neuroendocrinology
IS - 3
ER -