Mechanisms of Gender Differences in Exercise Capacity

The examination of gender differences has been a recent priority of the NIH. It is well documented that female rodents exhibit higher exercise capacity than their male counterparts. We confirmed this in C57 wild‐type(WT) mice, where female mice exhibited greater, p<0.05, maximal exercise capacity for running distance (469 ± 24 m) than age‐matched male WT mice (337 ± 14 m). The first goal was to examine whether these differences persisted with models of enhanced exercise capacity, e.g. exercise training and the adenylyl cyclase type 5 knockout (AC5 KO) mouse. When WT mice underwent chronic exercise‐training, female mice maintained their superiority over males, with females running a 32% greater distance (p<0.05) than age‐matched trained males. However, AC5 KO mice, which demonstrated enhanced exercise capacity, did not exhibit a gender difference, with female AC5 KO mice (695 ± 51 m) running similar distances to male AC5 KO mice (661 ± 45 m). The next goal was to determine mechanisms mediating these differences. After ovariectomy, WT female mice no longer demonstrated enhanced exercise compared with males. Conversely, chronic administration of estrogen to male mice improved their exercise performance and eliminated the gender differences with exercise. Next we investigated nitric oxide (NO), a downstream target of estrogen. Total NO synthase (NOS) activity was higher in female mice compared with male mice in both sedentary (207 ± 14 U/mg vs. 138 ± 4 U/mg, p<0.05) and exercise trained groups (338 ± 42 vs. 193 ± 15 U/mg, p<0.05). Ovariectomized females exhibited nitric oxide levels similar to males (165 ± 11 U/mg). Administration of L‐NAME, resulting in NO blockade, eliminated the gender differences in exercise performance. In AC5 KO mice NOS activity was not different in male and female mice and similar exercise performance in males and females was still observed after treatment with L‐NAME. Thus, both estrogen and nitric oxide are key mechanisms mediating the enhanced exercise performance in female mice. Support or Funding Information This study was supported by the National Institute of Health grant R01HL106511 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .