Estradiol alters body temperature regulation in the female mouse

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) 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 receptor signaling alters thermoregulation in the mouse. In this study, a method was developed to measure tail skin temperature (T) using a small data-logger attached to the surface of the tail, which, when combined with a telemetry probe for core temperature (T), allowed us to monitor thermoregulation in freely-moving mice over long durations. We report that estradiol treatment of ovariectomized mice reduced T during the light phase (but not the dark phase) while having no effect on T or activity. Estradiol also lowered T 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 during the dark phase. Subcutaneous injections of an NK receptor agonist (senktide) in ovariectomized mice caused an acute increase in T and a reduction in T, 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 receptor activation. Overall, we show that estradiol treatment of ovariectomized mice decreases T during the light phase, reduces the thermoregulatory effects of senktide and modulates thermoregulation differently than previously described in the rat.

Gonadal hormones influence core body temperature during calorie restriction

“…A different group of GNX female mice was implanted with 17-ß estradiol (E2) pellets (0.5 mg/21 d). Similar to what has been previously reported, estrogen replacement caused an immediate mild reduction of T b in gonadectomized female mice [20]. Compared to placebo, estrogen lowered T b by 0.3-0.5°C during the active phase of the day and by~0.5°C during the inactive phase of the day (Figure 4(a) and Supplementary Table 1).…”

“…Progesterone, estrogen, and androgen receptors have all been reported to be expressed in hypothalamic regions including the POA and to be able to influence T b [24][25][26][27][28][29]. Application of estradiol to the POA increased the firing rate of warm as well as some temperature-insensitive neurons and may contribute to explain of estradiol to lowers T b by increasing vasodilation and heat dissipation [20,30,31]; this reduction in T b is observed in our ad libitum data. Nevertheless, during CR, estradiol administration prevents T b reduction.…”

“…If the food would have been provided during the inactive phase of the day, most likely the animals would have experienced the hypothermic response during the active phase of the day. This would have affected their normal circadian T b profile, in which reduction of T b under ad libitum conditions occurs in the inactive phase of the day (lights on) [15,19,20]. Despite this qualitative similarity in T b reduction, females were more sensitive to this manipulation, displaying a deeper hypothermic response reaching~29.4°C that was evident as early as day 2 of 75% CR compared to male mice with a hypothermic response of~33.2°C (Figure 1(a-b)).…”

Hypothalamic estrogen receptor alpha mediates key side effects of tamoxifen therapy in mice

“…Telemetry data show 24-hour averages from the 2 telemetry sessions before and 3 weeks after tamoxifen or vehicle injections. Tail skin temperature was monitored every 5 min using a Nano-T temperature logger (Star-Oddi) that was attached to the ventral surface and 1 cm from the base of the tail in a 3D-printed polylactic acid collar modified from Krajewski-Hall et al(Krajewski-Hall et al 2018). Tail skin data show 24-hour averages for the same time periods as the telemetry data.…”

Influence of exogenous and endogenous estrogen on thermoregulatory responses to mild heat and the interaction with light and dark phases

“…Several studies have reported that estradiol (E 2 ) activates thermoregulatory mechanisms during exposure to heat in female rats [1][2][3][4][5]. Baker et al [1] demonstrated that, in the extreme heat of 38 °C, the increase in body temperature was greater in ovariectomized (OVX) rats than in OVX rats with E 2 replacement (OVX + E 2 ).…”