Short-term oxandrolone administration stimulates net muscle protein synthesis in young men

Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone [Oxandrin (OX)], a synt hetic analog of testosterone, would improve net muscle protein synthesis an d transport of amino acids across the leg. Six healthy men [22 +/- 1 (+/-SE ) yr] were studied in the postabsorptive state before and after 5 days of o ral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femor al arterio-venous sampling and muscle biopsy. The precursor-product method was used to determine muscle protein fractional synthetic rates. Fractional breakdown rates were also directly calculated. Total messenger ribonucleic acid (mRNA) concentrations of skeletal muscle insulin-like growth factor I and androgen receptor (AR) were determined using RT-PCR. Model-derived mus cle protein synthesis increased from 53.5 +/- 3 to 68.3 +/- 5 (mean +/- SE) nmol/min.100 mL/leg (P < 0.05), whereas protein breakdown was unchanged. I nward transport of amino acids remained unchanged with OX, whereas outward transport decreased (P < 0.05). The fractional synthetic rate increased 44% (P < 0.05) after OX administration, with no change in fractional breakdown rate. Therefore, the net balance between synthesis and breakdown became mo re positive with both methodologies (P < 0.05) and was not different from z ero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like gro wth factor I mRNA concentrations. We conclude that short term OX administra tion stimulated an increase in skeletal muscle protein synthesis and improv ed intracellular reutilization of amino acids. The mechanism for this stimu lation may be related to an OX-induced increase in AR expression in skeleta l muscle.