Role of dihydrotestosterone in whole-body energy utilization during acute running exercise in mice

[PURPOSE]: Dihydrotestosterone (DHT) plays an important role in various processes that utilize energy, including fat and carbohydrate oxidation. The purpose of this study was to determine the effect of inhibiting DHT formation during mid-intensity running exercise on energy expenditure and fat and carbohydrate oxidation in the whole body using a calorimetric chamber. [METHODS]: Twelve ICR adult male mice, 9 weeks of age, were randomized into two groups: CON (n = 6, no treatment with exercise) and CONIN (n = 6, DHT inhibitor treatment with exercise, SRD5A1A2 is an enzyme involved in the metabolism of free testosterone into DHT). Inhibitor was administered to the CONIN group intraperitoneally, while the CON group was treated with vehicle (corn oil 2 mg/kg). After 3 days of administration of the inhibitor or vehicle, exercise was performed at 60–70% VO(2)max for 30 min on a treadmill in a calorimetric chamber. The O(2) uptake, CO(2) production, carbohydrate and fat oxidation, and respiratory exchange ratio (RER) during 30-min exercise were measured using a calorimeter. [RESULTS]: During a single bout of exercise, the CONIN group showed a significantly higher area under the curve (AUC) of O(2) uptake and CO(2) production from 20 min into exercise than the CON group (p < 0.001). The CONIN group showed a significantly higher AUC for carbohydrate oxidation from 20 min into exercise than the CON group (p < 0.001), whereas no difference was found in fat oxidation between groups (p = 0.067). The CONIN group had a significantly higher AUC of RER from 20 min into exercise than the CON group (p < 0.001). [CONCLUSION]: We observed increased energy consumption at the later phase of 30-min moderate-intensity treadmill running when DHT production was inhibited. Furthermore, when DHT production during exercise was inhibited, whole-body fat utilization was inhibited and carbohydrate oxidation was substantially increased at the later phase of exercise compared to in the control group. Therefore, changes in DHT concentration in the body during exercise may be involved in whole-body fat utilization, suggesting that DHT may be an important factor affecting endurance exercise capacity.