Abstract
Hot flushes are due to estrogen withdrawal and characterized by the episodic activation of heat dissipation effectors. Recent studies (in humans and rats) have implicated neurokinin 3 (NK(3)) receptor signaling in the genesis of hot flushes. Although transgenic mice are increasingly used for biomedical research, there is limited information on how 17β-estradiol and NK(3) receptor signaling alters thermoregulation in the mouse. In this study, a method was developed to measure tail skin temperature (T(SKIN)) using a small data-logger attached to the surface of the tail, which, when combined with a telemetry probe for core temperature (T(CORE)), allowed us to monitor thermoregulation in freely-moving mice over long durations. We report that estradiol treatment of ovariectomized mice reduced T(CORE) during the light phase (but not the dark phase) while having no effect on T(SKIN) or activity. Estradiol also lowered T(CORE) in mice exposed to ambient temperatures ranging from 20 to 36°C. Unlike previous studies in the rat, estradiol treatment of ovariectomized mice did not reduce T(SKIN) during the dark phase. Subcutaneous injections of an NK(3) receptor agonist (senktide) in ovariectomized mice caused an acute increase in T(SKIN) and a reduction in T(CORE), consistent with the activation of heat dissipation effectors. These changes were reduced by estradiol, suggesting that estradiol lowers the sensitivity of central thermoregulatory pathways to NK(3) receptor activation. Overall, we show that estradiol treatment of ovariectomized mice decreases T(CORE) during the light phase, reduces the thermoregulatory effects of senktide and modulates thermoregulation differently than previously described in the rat.