PMID- 23150555
OWN - NLM
STAT- MEDLINE
DCOM- 20130219
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 48
DP  - 2012 Nov 27
TI  - Role for kisspeptin/neurokinin B/dynorphin (KNDy) neurons in cutaneous 
      vasodilatation and the estrogen modulation of body temperature.
PG  - 19846-51
LID - 10.1073/pnas.1211517109 [doi]
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 [NK(3)-saporin (SAP)] into the rat arcuate 
      nucleus. Remarkably, KNDy neuron ablation consistently reduced tail-skin 
      temperature (T(SKIN)), indicating that KNDy neurons facilitate cutaneous 
      vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation 
      blocked the reduction of T(SKIN) by 17beta-estradiol (E(2)), which occurred in the 
      environmental chamber during the light phase, but did not affect the E(2) 
      suppression of T(SKIN) during the dark phase. At the high ambient temperature of 
      33  degrees C, the average core temperature (T(CORE)) of ovariectomized (OVX) control 
      rats was significantly elevated, and this value was reduced by E(2) replacement. 
      In contrast, the average T(CORE) of OVX, KNDy-ablated rats was lower than OVX 
      control rats at 33  degrees C, and not altered by E(2) replacement. These data provide 
      unique evidence that KNDy neurons promote cutaneous vasodilatation and 
      participate in the E(2) 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.
FAU - Mittelman-Smith, Melinda A
AU  - Mittelman-Smith MA
AD  - Department of Pathology, University of Arizona College of Medicine, Tucson, AZ 
      85724, USA.
FAU - Williams, Hemalini
AU  - Williams H
FAU - Krajewski-Hall, Sally J
AU  - Krajewski-Hall SJ
FAU - McMullen, Nathaniel T
AU  - McMullen NT
FAU - Rance, Naomi E
AU  - Rance NE
LA  - eng
GR  - R01 AG032315/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20121112
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Kiss1 protein, rat)
RN  - 0 (Kisspeptins)
RN  - 86933-75-7 (Neurokinin B)
SB  - IM
MH  - Animals
MH  - *Body Temperature Regulation
MH  - Female
MH  - Kisspeptins/*physiology
MH  - Neurokinin B/*physiology
MH  - Neurons/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Skin/*blood supply
MH  - Tail/blood supply
MH  - Vasodilation/*physiology
PMC - PMC3511761
COIS- The authors declare no conflict of interest.
EDAT- 2012/11/15 06:00
MHDA- 2013/02/21 06:00
PMCR- 2012/11/12
CRDT- 2012/11/15 06:00
PHST- 2012/11/15 06:00 [entrez]
PHST- 2012/11/15 06:00 [pubmed]
PHST- 2013/02/21 06:00 [medline]
PHST- 2012/11/12 00:00 [pmc-release]
AID - 1211517109 [pii]
AID - 201211517 [pii]
AID - 10.1073/pnas.1211517109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19846-51. doi: 
      10.1073/pnas.1211517109. Epub 2012 Nov 12.