Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature

Melinda A. Mittelman-Smith, Hemalini Williams, Sally J. Krajewski-Hall, Nathaniel T. McMullen, Naomi E Rance

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Estrogen withdrawal in menopausal women leads to hot flushes, a syndrome characterized by the episodic activation of heat dissipation effectors. Despite the extraordinary number of individuals affected, the etiology of flushes remains an enigma. Because menopause is accompanied by marked alterations in hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons, we hypothesized that these neurons could contribute to the generation of flushes. To determine if KNDy neurons participate in the regulation of body temperature, we evaluated the thermoregulatory effects of ablating KNDy neurons by injecting a selective toxin for neurokinin-3 expressing neurons [NK3-saporin (SAP)] into the rat arcuate nucleus. Remarkably, KNDy neuron ablation consistently reduced tail-skin temperature (TSKIN), indicating that KNDy neurons facilitate cutaneous vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation blocked the reduction of TSKIN by 17β-estradiol (E2), which occurred in the environmental chamber during the light phase, but did not affect the E2 suppression of TSKIN during the dark phase. At the high ambient temperature of 33 °C, the average core temperature (TCORE) of ovariectomized (OVX) control rats was significantly elevated, and this value was reduced by E 2 replacement. In contrast, the average TCORE of OVX, KNDy-ablated rats was lower than OVX control rats at 33 °C, and not altered by E2 replacement. These data provide unique evidence that KNDy neurons promote cutaneous vasodilatation and participate in the E2 modulation of body temperature. Because cutaneous vasodilatation is a cardinal sign of a hot flush, these results support the hypothesis that KNDy neurons could play a role in the generation of flushes.

Original languageEnglish (US)
Pages (from-to)19846-19851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number48
DOIs
StatePublished - Nov 27 2012

Fingerprint

Neurokinin B
Kisspeptins
Dynorphins
Body Temperature
Vasodilation
Estrogens
Neurons
Skin
Skin Temperature
Tail
Hot Temperature
Arcuate Nucleus of Hypothalamus
Temperature
Body Temperature Regulation
Menopause
Estradiol

Keywords

  • Gonadotropin-releasing hormone
  • Reproduction
  • Thermoregulation

ASJC Scopus subject areas

  • General

Cite this

Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. / Mittelman-Smith, Melinda A.; Williams, Hemalini; Krajewski-Hall, Sally J.; McMullen, Nathaniel T.; Rance, Naomi E.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 109, No. 48, 27.11.2012, p. 19846-19851.

Research output: Contribution to journalArticle

Mittelman-Smith, Melinda A. ; Williams, Hemalini ; Krajewski-Hall, Sally J. ; McMullen, Nathaniel T. ; Rance, Naomi E. / Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous vasodilatation and the estrogen modulation of body temperature. In: Proceedings of the National Academy of Sciences of the United States of America. 2012 ; Vol. 109, No. 48. pp. 19846-19851.
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AU - McMullen, Nathaniel T.

AU - Rance, Naomi E

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AB - Estrogen withdrawal in menopausal women leads to hot flushes, a syndrome characterized by the episodic activation of heat dissipation effectors. Despite the extraordinary number of individuals affected, the etiology of flushes remains an enigma. Because menopause is accompanied by marked alterations in hypothalamic kisspeptin/neurokinin B/dynorphin (KNDy) neurons, we hypothesized that these neurons could contribute to the generation of flushes. To determine if KNDy neurons participate in the regulation of body temperature, we evaluated the thermoregulatory effects of ablating KNDy neurons by injecting a selective toxin for neurokinin-3 expressing neurons [NK3-saporin (SAP)] into the rat arcuate nucleus. Remarkably, KNDy neuron ablation consistently reduced tail-skin temperature (TSKIN), indicating that KNDy neurons facilitate cutaneous vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation blocked the reduction of TSKIN by 17β-estradiol (E2), which occurred in the environmental chamber during the light phase, but did not affect the E2 suppression of TSKIN during the dark phase. At the high ambient temperature of 33 °C, the average core temperature (TCORE) of ovariectomized (OVX) control rats was significantly elevated, and this value was reduced by E 2 replacement. In contrast, the average TCORE of OVX, KNDy-ablated rats was lower than OVX control rats at 33 °C, and not altered by E2 replacement. These data provide unique evidence that KNDy neurons promote cutaneous vasodilatation and participate in the E2 modulation of body temperature. Because cutaneous vasodilatation is a cardinal sign of a hot flush, these results support the hypothesis that KNDy neurons could play a role in the generation of flushes.

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