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

Departments ¹Biomedical Sciences, ²Physical Therapy, ³Biochemistry, ⁴Child Health, and ⁵Animal Sciences, University of Missouri, Columbia, Missouri 65211

Submitted 14 August 2008 ; accepted in final form 27 January 2009

Estrogen (E₂) is reported to regulate skeletal muscle mass and contractile function; whether E₂ exerts its effects through estrogen receptor- (ER) or -β (ERβ) is unclear. We determined the effect of ER 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 E₂ elimination effects on muscle, we also used aromatase (Ar) knockout (KO) and wild-type (WT) mice. ER 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 ER (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 KO was lower in TA and Gast than in WT. Lower P_o/aCSA in ER KO Gast and TA was also supported histologically by significantly less P_o/fiber areas (P < 0.05). ArKO mice also had lower P_o/aCSA in Gast and TA compared with WT. ERβ 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 ER but that E₂ effects may be mediated via more than one mechanism or receptor.

muscle mass; peak tetanic tension; fiber area; myosin protein