Differences in tolerance to exertional hyperthermia between male and female mice

Abstract

Surveillance reports suggest possible reductions in heat stroke susceptibility in female vs. male active component members of the US Armed Forces, but whether these differences reflect behavior or underlying biology is unknown. Previous studies in mice have shown that females exhibit markedly better resistance to moderate, passive heat. However, whether heat tolerance translates to acute settings or to exertional heat stroke (EHS) has not been tested. In this study, we compared responses in male and female mice to an established model of EHS. Exercise trained mice (3 wks) were maintained at 37.5°C (35% RH) and ran using a preprogrammed incremental protocol on a forced running wheel. The EHS end point was defined as loss of consciousness. Female mice on average ran longer than males (177 vs. 124 min; p=0.0001), and were exposed to greater heat loads (241 vs. 160 °C • min; p=0.0001). Male and female mice ran to nearly identical average peak core temperatures, both 42.2°C (n.s.). There were no differences in the minimum temperature during post EHS hypothermia 32°C (n.s.) or the time to reach the minimum temperature. However, females lost a greater % body weight (9.2% vs 7.5% p < 0.001), demonstrated significantly higher levels of circulating corticosterone (286 vs 183 ng/ml, p = 0.001, 3 h) and higher levels of resistin polypeptide (8891 vs. 3781 pg/ml, p = 0.004, 3 h). These results demonstrate that female mice have greater resistance to EHS during exercise in hyperthermia. Possible mechanisms include greater body surface to mass ratio in females vs. males (3.3 vs. 3.2 m2/kg; p=0.0001), greater aerobic conditioning in females (characteristic of mice), or a hormonally or genetically induced resistance to hyperthermia. Though controversial, marked elevations in circulating corticosterone and resistin in females have the capacity to contribute to improved heat tolerance. We conclude that female mice are significantly more resistant to EHS than male mice. Inherent thermal tolerance in female mice may provide an evolutionary advantage because metabolic rate and heat production have been shown to double during pregnancy and lactation. Author views not official US Army or DoD policy. W81XWH‐15‐2‐0038