AuthorDacks, Penny Ann Frances
AdvisorRance, Naomi E.
Committee ChairRance, Naomi E.
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractApproximately 75% of menopausal women in the United States experience hot flushes but the etiology of this thermoregulatory disorder is unknown. The dominant theory is that estrogen withdrawal sensitizes thermoregulatory areas of the brain, leading to the inappropriate activation of heat loss effectors in response to mild stimuli. This dissertation examines the circuitry of estrogen effects on thermoregulation. First, a rodent model was characterized. In ovariectomized rats, estradiol treatment decreased tail skin vasodilatation, a primary heat loss mechanism, and raised the ambient temperature threshold for tail skin vasodilatation. These results indicate that estradiol does not alter the maximal ability of blood vessels to constrict and dilate, but rather shifts the threshold for thermoregulatory activation in rats. Using this animal model, we examined how estradiol treatment and ambient temperature affect neuronal activity in brain areas involved with thermoregulation and reproduction. Out of 14 examined regions, only 3 areas were significantly affected by both estradiol and temperature and only the median preoptic nucleus (MnPO) exhibited increased activity at warmer ambient temperature. Interestingly, the effects of estradiol and ambient temperature on MnPO activity closely resembled their effects on tail skin vasodilatation. These results identify the MnPO as a plausible site for the integration of estrogen with skin vasodilatation. In the third study, we examined whether thermoregulation can be modified by neurokinin 3 (NK3) receptors, the dominant receptor for neurokinin B (NKB). Core temperature in ovariectomized rats was decreased by microinfusion of a selective NK3 receptor agonist into the MnPO and adjacent septal areas. This transient hypothermia was accompanied by a lack of homeostatic tail skin vasoconstriction but was not caused by tail skin vasodilatation or a global impairment in thermoregulation. These results demonstrate that thermoregulation in rats is modified by NK3 receptors in brain areas that receive projections from NKB neurons. In humans, menopause is associated with hot flushes and the hypertrophy and increased NKB gene expression in arcuate (infundibular) neurons. We propose a novel theory that estrogen withdrawal causes hot flushes by enhancing NKB release from arcuate (infundibular) neurons onto NK3 receptors.