Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb muscle mass and contractile function in female mice.

Estrogen (E2) is reported to regulate skeletal muscle mass and contractile function; whether E2 exerts its effects through estrogen receptor-alpha (ERalpha) or -beta (ERbeta) is unclear. We determined the effect of ERalpha or ERbeta elimination on muscle mass and contractile function in multiple muscles of the lower limb, muscles with different locomotor tasks and proportions of fiber types I and II: soleus (Sol), plantaris (Plan), tibialis anterior (TA), and gastrocnemius (Gast) in mature female mice. To determine E2 elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ERalpha and ArKO body weights were approximately 10 and 20% higher than WT. Although muscle mass tended to show a commensurate increase in both groups, only the TA was significantly larger in ERalpha (P<0.05). Ratios of muscle mass to body mass revealed significantly lower values for Gast and TA in ArKO mice (P<0.05). Tetanic tension (Po) per calculated anatomical cross-sectional area (aCSA) in ERalpha KO was lower in TA and Gast than in WT. Lower Po/aCSA in ERalpha KO Gast and TA was also supported histologically by significantly less Po/fiber areas (P<0.05). ArKO mice also had lower Po/aCSA in Gast and TA compared with WT. ERbeta KO and WT mice were comparable in all measures. Our results support the hypothesis that E2 effects on skeletal muscle are mediated in part via the ERalpha but that E2 effects may be mediated via more than one mechanism or receptor.