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

Abstract

Estrogen (E2) is reported to regulate skeletal muscle mass and contractile function; whether E2exerts its effects through estrogen receptor-α (ERα) or -β (ERβ) is unclear. We determined the effect of ERα or ERβ 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 E2elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ERα and ArKO body weights were ∼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 ERα ( 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 ERα KO was lower in TA and Gast than in WT. Lower Po/aCSA in ERα 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. ERβ KO and WT mice were comparable in all measures. Our results support the hypothesis that E2effects on skeletal muscle are mediated in part via the ERα but that E2effects may be mediated via more than one mechanism or receptor.