Endocrine Abstracts

The predominant positive and negative regulators of skeletal muscle mass are IGF1 and myostatin respectively. The regulation of skeletal muscle mass, IGF1 and myostatin by the gonadal steroids testosterone and 17β-oestradiol (E₂) remains controversial. Male and female C57BL/6 mice underwent bilateral gonadectomy or sham surgery at 4 weeks of age, with insertion of s.c. silastic implants containing testosterone, E₂, or cholesterol (placebo) (n=8/treatment and sex). Blood and hindlimb muscles were collected at 13 weeks of age and muscle mass was normalised to bone length. Concentrations of IGF1 in plasma were determined by ELISA. C2C12 myoblasts were treated under differentiating conditions with testosterone (30 nM) or E₂ (10 nM) for 24 h and RNA was harvested for quantitative PCR. Myoblasts were also treated for 96 h and differentiation was assessed by immunocytochemistry. Sexual dimorphism of normalised hindlimb muscle mass was lost post-gonadectomy. In male mice, gonadectomy reduced normalised hindlimb muscle mass, reduced IGF1 mRNA expression and increased mature myostatin protein abundance (P<0.001). Replacement of testosterone normalised these parameters, while replacement of E₂ only normalised hindlimb muscle mass. Concentrations of IGF1 in plasma were not altered by any treatment in males. In female mice, gonadectomy±E₂ replacement did not alter normalised hindlimb muscle mass or mature myostatin protein abundance, despite reducing concentrations of IGF1 in plasma and skeletal muscle (P<0.05). Testosterone significantly increased normalised hindlimb muscle mass, increased concentrations of IGF1 in plasma and skeletal muscle, while reducing the abundance of mature myostatin. Testosterone significantly increased myotube hypertrophy (151%) to a greater extent than E₂ (61%); although, neither altered IGF1 mRNA expression. We conclude that the anabolic action of testosterone on skeletal muscle is partially through modulation of IGF1 and myostatin activity. However, E₂ appears to increase skeletal muscle mass independently of IGF1 or myostatin.

Disclosure: Waikato Medical Research Foundation (grant number 223).