Effects of estradiol on the thermoneutral zone and core temperature in ovariectomized rats

Abstract

Hot flushes represent a disorder of central thermoregulation characterized by the episodic activation of heat loss mechanisms. Although flushes are associated with estrogen withdrawal, there is little understanding of the effects of estrogen on thermoregulation in any species. It has been proposed that hormone withdrawal increases the sensitivity of hypothalamic neural pathways that control heat dissipation effectors. If so, we predicted that ovariectomized rats without estradiol treatment would activate tail skin vasodilatation (a major heat loss effector) at lower ambient temperatures and thereby lower the thermoneutral zone. The thermoneutral zone, defined as the range of ambient temperatures in which thermoregulation is achieved only by sensible (dry) heat loss, was evaluated based on properties of skin vasomotion. Core and tail skin temperatures were recorded in ovariectomized rats (with and without estradiol-17beta) exposed to ambient temperatures from 13 to 34 C in an environmental chamber. Rats without estradiol exhibited increased skin vasodilatation and a shift in the thermoneutral zone to lower ambient temperatures. Moreover, the ambient temperature threshold for skin vasodilatation was significantly lower in rats without estradiol treatment. At most ambient temperatures, average core temperature was unaffected by estradiol. However, at ambient temperatures of 32.5 C and above, untreated ovariectomized rats exhibited higher core temperatures compared with estradiol-treated rats. Thus, estradiol-17beta treatment enhanced the maintenance of core temperature during heat exposure. These findings support the hypothesis that estrogen withdrawal increases the sensitivity of thermoregulatory neural pathways and modifies the activation of heat loss mechanisms.

Figure 1

T_CORE (A) and HLI (B) of OVX and OVX+E rats at T_AMBIENT from 13 to 34 C. Values represent mean ± sem (n = 11–12 rats/group). A, At most T_AMBIENT, estradiol-17β had no effect on average T_CORE. However, at T_AMBIENT above 32.5 C, the T_CORE of OVX rats was significantly higher than OVX+E rats. B, The overall average HLI was significantly decreased by estradiol treatment (two-way repeated ANOVA). *, Specific T_AMBIENT at which OVX and OVX+E was significantly different, based on post hoc tests (P < 0.05).

Figure 2

Criterion 1 (A, HLI range) and criterion 2 (B, middleness index) used to evaluate the thermoneutral zone of OVX and OVX+E rats at T_AMBIENT from 13 to 34 C. The open or filled circles represent median values (n = 11–12 rats/group). The straight line and parabola were fitted to these points using breakpoint analysis. The range of the parabola approximates the thermoneutral zone. The first breakpoint from the straight line to the parabola was at significantly lower T_AMBIENT in OVX rats compared with OVX+E rats for both criterion 1 and 2. These findings indicate a lower T_AMBIENT threshold for activation of cutaneous vasomotion in OVX rats without estradiol-17β treatment. *, Nonoverlapping 95% confidence intervals comparing the first breakpoint for OVX vs. OVX+E rats.