Regulation of skeletal muscle strength by estradiol: neuronal nitric oxide synthase and myosin regulatory light chain

Abstract

Loss of skeletal muscle strength is a significant health concern with aging. In women, increased loss of strength happens during menopause, suggesting that the loss is related to changes in ovarian hormones. Estradiol, a predominant hormone secreted by ovaries, plays an important role in the function of the key contractile protein, myosin, and thus muscle strength in young adult, female mice. However, the mechanism(s) by which estradiol affects strength in females is not known. The goal of this study is to elucidate the mechanism of estradiol on musculoskeletal strength in female mice. We found the expression of neuronal nitric oxide synthase (nNOS) and the phosphorylation of myosin regulatory light chain (RLC) in muscles of ovariectomized mice were reduced 52–74%, compared to ovary intact‐mice (P<0.001). Estradiol treatment reversed the expression of nNOS and phosphorylation of RLC. In addition, reduced nNOS activity resulted in decreased phosphorylation of RLC. Using a complementary C2C12 cell culture approach, we found that these effects are mediated by estrogen receptor beta (ERß). These results indicate that estradiol regulates skeletal muscle nNOS expression and RLC phosphorylation through ERß, which in turn may contribute to changes in muscle strength in females.