Estradiol alters body temperature regulation in the female mouse

Figures & data

Figure 1. Photographs of the Delrin plastic housing and cap unassembled (A) and assembled (B) with a Star-Oddi DST nano-T probe. A clear window in at the end of the probe allowed the temperature sensor to be oriented toward the ventral surface of the tail. The housing was glued on each side of the tail at a consistent distance from the base (C & D). E, A representative graph from an individual OVX mouse shows wide fluctuations in T_SKIN. The dark phase is indicated by black bars. Scale bar in A = 10 mm, applies to A.

Figure 2. Protocols of Exp. 1–3 (A) and Exp. 4 (B). A, Mice were ovariectomized (OVX) and one week later received s.c. capsules containing 180 µg/mL E₂ or vehicle. Circadian rhythms of T_CORE, T_SKIN and activity were recorded over a 5 day period with mice in their home cages. From days 13–21, the mice were exposed to various T_AMBIENT in an environmental chamber. The next day, mice were injected s.c. with either senktide or vehicle. Mice received a second injection two days later in a crossover design. B, Protocol of Exp. 4. Ten mice were OVX and 15 days later implanted with s.c. capsules containing 360 µg/mL E₂. The capsules were removed after 7 days and after a wash out period, the mice were implanted with capsules containing 720 µg/mL E₂. Circadian rhythms of T_CORE, T_SKIN and activity were recorded for 3 day intervals in the animals home cages (grey bars). Black arrowheads, OVX; grey arrowheads, capsule implants; open arrowheads, blood sample collection. E₂, 17β-estradiol; OVX, ovariectomized; VEH, vehicle.

Figure 3. E₂ treatment of OVX mice reduces T_CORE during the light phase (A, B) with no significant effect on T_SKIN (C, D), heat loss index (E, F) or activity (G, H). The line graphs (left) show the mean values for each group 3 to 5 days after E₂ treatment. The lines are generated with a moving average of 5 points and the black bars on the X axis denote the dark phase. The bar graphs (right) show data analysis (mean ± SEM) from days 3–5. Light vs dark phase differences were identified (B, D, F, H), except for T_SKIN in the OVX + E₂ group (D). Unlike previous studies in the rat, E₂ did not decrease T_SKIN or HLI in the dark phase. n = 9 – 10 mice/group, + Significantly different OVX vs OVX + E₂, p = 0.02, * Significantly different light vs dark within treatment group, p < 0.01, ** Significantly different light vs dark within treatment group, p < 0.001.

Table 1. Treatment of OVX mice with higher concentrations of E₂ reduces T_CORE during the light phase, with no effect on T_SKIN, HLI or activity.

	Phase	OVX	360 µg/mL E2	720 µg/mL E2
TCORE (°C)	Light	36.6 ± 0.04^*	36.3 ± 0.07^*^+	36.3 ± 0.05^*^+
	Dark	37.6 ± 0.07	37.7 ± 0.09	37.6 ± 0.06
TSKIN (°C)	Light	31.4 ± 0.32^*	30.5 ± 0.22	31.5 ± 0.38^*
	Dark	29.8 ± 0.46	29.2 ± 0.15	30.1 ± 0.48
HLI	Light	0.63 ± 0.02^*	0.58 ± 0.01^*	0.65 ± 0.03^*
	Dark	0.49 ± 0.03	0.47 ± 0.01	0.50 ± 0.03
Activity (counts)	Light	269.8 ± 35.0^*	243.7 ± 41.9^*	166.5 ± 21.9^*
	Dark	652.0 ± 54.0	675.8 ± 92.8	705.2 ± 65.0

Average (±SEM) core temperature (T_CORE), tail skin temperature (T_SKIN), heat loss index and summed activity counts of OVX mice receiving different doses of E₂.

n = 10 mice/group.

* , significantly different, light vs. dark phase, within treatment group, p < 0.01.⁺, significantly different, compared to OVX, within light phase, p < 0.02.

Figure 4. Effects of E₂ treatment on T_CORE (A), T_SKIN (B), HLI (C) and HLI variability (D) in OVX mice exposed to T_AMBIENT ranging from 20–36°C. A, T_CORE was lower in E₂ treated mice at a wide range of T_AMBIENT. At 35 and 36°C the T_CORE was significantly elevated in both groups. B and C, At select T_AMBIENT, both T_SKIN and HLI were significantly lower in OVX + E₂ mice. D, At the high T_AMBIENT of 34–36°C, HLI variability is reduced, reflecting constant vasodilation to dissipate body heat. n = 9 – 10 mice/group. * Significantly different OVX vs OVX+E₂, p < 0.05, + Significantly different than the majority of values at the other T_AMBIENT, p < 0.05.

Figure 5. Average T_CORE (A), T_SKIN (B), heat loss index (C) and activity (D) during the estrous cycle of the mouse. Circadian rhythms were observed but there was no effect of the phase of the estrous cycle. Values represent mean ± SEM, n = 16 cycles averaged from 6 mice. + Significantly different than light phase p < 0.05, * Significantly different than light phase p < 0.01.

Figure 6. Effects of s.c. injections of the NK₃ receptor agonist senktide (or vehicle) on T_CORE (top) and T_SKIN (bottom) in OVX (left) and OVX + E₂ (right) treated mice. Senktide acutely lowered T_CORE (A) and increased T_SKIN (C) in OVX mice. In OVX + E₂ treated mice, the T_CORE reduction after senktide was blunted (B) and the acute rise in T_SKIN did not occur (D). Values represent mean ± SEM, 0 = time of injection, A and B, n = 9 – 10 mice/group; C, n = 5 mice; D, n = 7 mice, * Significantly different from vehicle, p < 0.01 (T_CORE) or 0.05 (T_SKIN).