Sexual dimorphism in the response of muscle and bone to myostatin (GDF8) deficiency

Abstract

Males and females show marked differences in the deposition and modeling of bone during growth. Increased levels of testosterone in males are associated with increased muscle mass and periosteal expansion, whereas increased levels of estrogen in females are associated with endosteal contraction. Myostatin-deficiency increases muscle mass and bone density, and we proposed that the response of muscle and bone to loss of myostatin function may be affected by sex hormone status. We tested this hypothesis by measuring body weight, triceps brachii mass, and bone biomechanical properties of the radius in male and female wild-type and myostatin-deficient mice, 4 months of age (n=12/group). Two-factor ANOVA with sex and genotype as the two factors was used to test for significant interactions between sex and genotype for all variables. Significant sex-genotype interactions were detected for body mass, muscle mass, bone diameter, cortical thickness, area moment of inertia, and ultimate bone stress and strain, with males showing a greater response to myostatin deficiency than females for each variable. These data indicate that downregulation of myostatin produces a greater anabolic response in male skeletal muscle than in female muscle. Moreover, sex-specific differences in the response of muscle to myostatin deficiency in turn yield sex-specific differences in bone shape and biomechanical properties. These findings suggest that molecular therapies aimed at increasing muscle and bone strength via myostatin blockade may be more effective in men than in women. Funding for this research was provided by the National Institutes of Health (NIAMS AR049717-01A2).