Skeletal Muscle Specific Knock out of Estrogen Receptor Alpha Results in Low Strength

Abstract

Previous studies from our lab and others have shown that estradiol deficiency in rodents and post-menopausal women results in skeletal muscle strength deficits. There are three known estrogen receptors (ERalpha, ERbeta, and GPER30) and estrogen is known to elicit its effects through estrogen receptors in other tissues. Whole body ERalpha knockout mice exhibit metabolic disorders with little known regarding the specific role of estrogen receptor alpha in skeletal muscle. PURPOSE: To identify the impact of ERalpha on skeletal muscle in vivo contractile function. METHODS: ERalpha flox mice were crossed with Human Skeletal Muscle (HSA) cre mice to create a skeletal muscle specific ERalpha knockout mouse (skmERαKO). Muscle strength of the posterior crural muscles of 4–6 month female skmERαKO mice and wild type (WT) littermates was assessed in isoflurane-anesthetized mice. RESULTS: There was no effect of skeletal muscle ERalpha knockout on body mass. Skeletal muscle knockout of ERalpha results in weaker muscles. Posterior crural muscles of skmERαKO mice exhibit 14% lower peak isometric torque and 16% lower peak concentric torque than skmERαWT mice (p<0.01). Additionally, higher stimulation frequencies are required to generate torque in skmERαKO mice compared to skmERαWT mice with 50% maximal torque being reached at 47 Hz for skmERαKO mice and 43 Hz for WT mice (p=0.042). Finally, power at low velocity was 15% lower in skmERαKO mice compared to skmERαWT mice (p=0.029). CONCLUSIONS: ERalpha plays an important role in skeletal muscle strength. Ablation of ERalpha in skeletal muscle results in muscles that produce less torque and power. This research was supported by NIH grant R01-AG031743 and American Diabetes Association grant (EES). TLM was supported by University of Minnesota Doctoral Dissertation Fellowship. BCC was supported by T32-AR07612.