Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 48, Pages 19846-19851Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1211517109
Keywords
reproduction; gonadotropin-releasing hormone; thermoregulation
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Funding
- National Institutes of Health, National Institute on Aging Grant [R01 AG032315]
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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 (T-SKIN), indicating that KNDy neurons facilitate cutaneous vasodilatation, an important heat dissipation effector. Moreover, KNDy ablation blocked the reduction of T-SKIN by 17 beta-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.
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