We have studied the effect of a pharmacological dose of testosterone enanthate (3 --1 for 12 wk) on muscle mass and total-body potassium and on whole-body and muscle protein synthesis in normal male subjects. Muscle mass estimated by creatinine excretion increased in all nine subjects (20% mean increase, P less than ); total body potassium mass estimated by 40K counting increased in all subjects (12% mean increase, P less than ). In four subjects, a primed continuous infusion protocol with L-[1-13C]leucine was used to determine whole-body leucine flux and oxidation. Whole-body protein synthesis was estimated from nonoxidative flux. Muscle protein synthesis rate was determined by measuring [13C]leucine incorporation into muscle samples obtained by needle biopsy. Testosterone increased muscle protein synthesis in all subjects (27% mean increase, P less than ). Leucine oxidation decreased slightly (17% mean decrease, P less than ), but whole-body protein synthesis did not change significantly. Muscle morphometry showed no significant increase in muscle fiber diameter. These studies suggest that testosterone increases muscle mass by increasing muscle protein synthesis.
In 209 community-dwelling men with low T levels (100 to 350 ng/dL [ to nmol/L]) from Testosterone in Older Men (TOM) with Mobility Limitations Trial, the daily T gel therapy for 6 months improved both leg-press and chest-press strength and stair-climbing power [ 65 ]. Testosterone may also influence muscle metabolism by improving haemoglobin levels in older men with mild anaemia [ 66 , 67 ]. In women, skeletal muscle tissue seems to be sensitive to the anabolic action of androgens [ 68 ]. However, the impact of T administration on full physical function has not been fully studied. The precise molecular mechanisms underlying these observed physical changes in men are likely to include specific T effects on adipocytes and skeletal muscle cell receptors. The binding of T to its receptors could lead to the stimulation of lipolysis and protein synthesis [ 41 , 69 ]. Finally, several lines of evidence support the hypothesis of permissive effects of T on the differentiation of the precursor stromal cells into muscular line [ 70 ].
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