Testosterone mediates hyperthermic response of mice to heat exposure

Abstract

AimsTestosterone is implicated as a potential contributing factor to heat-induced injury. We examined effects of testosterone on thermal response of mice to heat exposure. Main methodsAdult C57BL/6J male mice received gonadectomy or sham surgery subsequent vehicle (Gnx) or testosterone implants (Gnx+T). Body core temperature (Tc) of mice was recorded telemetrically during acute heat exposure. Thermal responses to heat exposure were also examined in age-matched female mice at each stage of the estrous cycle. Key findingsBasal Tc was lower in sham male mice than females, but did not differ among sham, Gnx or Gnx+T males. No alterations in expression of uncoupling proteins 2 and 3 in the gastrocnemius muscle were found in either Gnx or Gnx+T mice compared to sham males. During heat exposure, sham male mice had a faster and greater rise in Tc, compared to females. This rapid hyperthermic response to heat was abolished in Gnx males, but not in Gnx+T males. No significant correlation was revealed between peak Tc values and plasma testosterone concentrations in Gnx+T males treated with either low- or high-dose testosterone. No effects of estrous cycle phase on the thermal response to heat exposure were detected in female mice. SignificanceWe found that male mice were more susceptible to development of heat-induced hyperthermia than females and this was prevented by castration, not by castration with testosterone replacement. These results suggest that testosterone mediates heat-induced hyperthermia and is a heat stress susceptibility factor.