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1 Division of Endocrinology, Metabolism, and Molecular Medicine, Chalres R. Drew University of Medicine and Sciences, Los Angeles, CA, USA
2 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: sbhasin{at}ucla.edu.
Testosterone (T) supplementation in men induces muscle fiber hypertrophy; we hypothesized that T-induced increase in muscle fiber size is associated with a dose-dependent increase in satellite cell number. We quantitated satellite cell and myonuclear number by using direct counting and spatial orientation methods in biopsies of vastus lateralis obtained at baseline and after 20-weeks of treatment with a GnRH agonist and 125, 300, or 600-mg weekly dose of T enanthate. Testosterone administration was associated with a significant increase in myonuclear number in men receiving 300 and 600 mg doses. The post-treatment, percent satellite cell number, obtained by direct counting, differed significantly among the 3 groups (ANCOVA P<0.000001); the mean post-treatment values (5.0 and 15.0%) in men treated with 300- and 600-mg doses were greater than baseline (2.5 and 2.5%, respectively, P<0.05 vs. baseline). The absolute satellite cell number measured by spatial orientation at 20 weeks (1.5 and 4.0 per mm) was significantly greater than baseline (0.3 and 0.6 per mm) in men receiving the 300- and 600-mg doses (P<0.05). The change in percent satellite cell number correlated with changes in total (r= 0.548) and free T concentrations (r=0.468). Satellite cell and mitochondrial areas were significantly higher and the nuclear to cytoplasmic ratio lower after treatment with 300- and 600-mg doses. Conclusion: T-induced muscle fiber hypertrophy is associated with an increase in satellite cell number, a proportionate increase in myonuclear number, and changes in satellite cell ultrastructure.
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