Ablation of skeletal muscle estrogen receptor alpha impairs contractility in male mice

Estradiol and estrogen receptor a (ERa) have been shown to be important for the maintenance of skeletal muscle strength in females; however, little is known about the roles of estradiol and ERa in male muscle. The purpose of this study was to determine if skeletal muscle ERa is required for optimal contractility in male mice. We hypothesize that reduced ERa in skeletal muscle impairs contractility in male mice. Skeletal muscle-specific knockout (skmERaKO) male mice exhibited reduced strength across multiple muscles and several contractile parameters related to force generation and kinetics compared with wild-type littermates (skmERaWT). Isolated EDL muscle-specific isometric tetanic force, peak twitch force, peak concentric and peak eccentric forces, as well as the maximal rates of force development and relaxation were 11%–21% lower in skmERaKO compared with skmERaWT mice. In contrast, isolated soleus muscles from skmERaKO mice were not affected. In vivo peak torque of the anterior crural muscles was 20% lower in skmERaKO compared with skmERaWT mice. Muscle masses, contractile protein contents, fiber types, phosphorylation of the myosin regulatory light chain, and caffeine-elicited force did not differ between muscles of skmERaKO and skmERaWT mice, suggesting that strength deficits were not due to size, composition, or calcium release components of muscle contraction. These results indicate that in male mice, reduced skeletal muscle ERa blunts contractility to a magnitude similar to that previously reported in females; however, the mechanism may be sexually dimorphic. NEW & NOTEWORTHY We comprehensively measured in vitro and in vivo contractility of leg muscles with reduced estrogen receptor a (ERa) in male mice and reported that force generation and contraction kinetics are impaired. In contrast to findings in females, phosphorylation of myosin regulatory light chain cannot account for low force production in male skeletal muscle ERa knockout mice. These results indicate that ERa is required for optimal contractility in males and females but via sexually dimorphic means.