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

Estradiol and estrogen receptor α (ERα) 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 ERα in male muscle. The purpose of this study was to determine if skeletal muscle ERα is required for optimal contractility in male mice. We hypothesize that reduced ERα in skeletal muscle impairs contractility in male mice. Skeletal muscle specific knockout (skmERαKO) male mice exhibited reduced strength across multiple muscles and several contractile parameters related to force generation and kinetics compared to wildtype littermates (skmERαWT). 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 skmERαKO compared to skmERαWT mice. In contrast, isolated soleus muscles from skmERaKO mice were not affected. In vivo peak torque of the anterior crural muscles were 20% lower in skmERαKO compared to skmERαWT 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 skmERαKO and skmERαWT 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 ERα blunts contractility to a magnitude similar to that previously reported in females, however, the mechanism may be sexually dimorphic.