Estrogen receptor-α and -β and aromatase knockout effects on lower limb muscle mass and contractile function in female mice

Brown M, Ning J, Ferreira JA, Bogener JL, Lubahn DB. Estrogen receptor-alpha and -beta and aromatase knockout effects on lower limb muscle mass and contractile function in female mice. Am J Physiol Endocrinol Metab 296: E854-E861, 2009. First published January 27, 2009; doi:10.1152/ajpendo.90696.2008.-Estrogen (E(2)) is reported to regulate skeletal muscle mass and contractile function; whether E(2) exerts its effects through estrogen receptor-alpha (ER alpha) or -beta (ER beta) is unclear. We determined the effect of ER alpha or ER beta 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. ER alpha and ArKO body weights were similar to 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 ER alpha (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 (P(o)) per calculated anatomical cross-sectional area (aCSA) in ER alpha KO was lower in TA and Gast than in WT. Lower P(o)/aCSA in ER alpha KO Gast and TA was also supported histologically by significantly less P(o)/fiber areas (P < 0.05). ArKO mice also had lower Po/aCSA in Gast and TA compared with WT. ER beta KO and WT mice were comparable in all measures. Our results support the hypothesis that E(2) effects on skeletal muscle are mediated in part via the ER alpha but that E(2) effects may be mediated via more than one mechanism or receptor.