Estradiol alters body temperature regulation in the female mouse

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 (NK₃) 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 NK₃ 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 NK₃ 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 NK₃ 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.