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The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 8 2705-2711
Copyright © 1999 by The Endocrine Society


From the Clinical Research Centers

Short-Term Oxandrolone Administration Stimulates Net Muscle Protein Synthesis in Young Men1

Melinda Sheffield-Moore, Randall J. Urban, Steven E. Wolf, J. Jiang, Don H. Catlin, David N. Herndon, Robert R. Wolfe and Arny A. Ferrando

Departments of Surgery (M.S.-M., S.E.W., D.N.H., R.R.W., A.A.F.), Anesthesiology (R.R.W.), and Internal Medicine (R.J.U., J.J.), University of Texas Medical Branch, and Shriners Burn Hospital for Children (D.N.H., R.R.W.), Galveston, Texas 77550; and the Department of Molecular and Medical Pharmacology, University of California, Olympic Analytical Laboratory (D.H.C.), Los Angeles, California 90025

Address all correspondence and requests for reprints to: Melinda Sheffield-Moore, Ph.D., Metabolism Unit, Shriners Burns Institute, 815 Market Street, Galveston, Texas 77550. E-mail: melmoore{at}utmb.edu

Short term administration of testosterone stimulates net protein synthesis in healthy men. We investigated whether oxandrolone [Oxandrin (OX)], a synthetic analog of testosterone, would improve net muscle protein synthesis and 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 oral OX (15 mg/day). Muscle protein synthesis and breakdown were determined by a three-compartment model using stable isotopic data obtained from femoral 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 muscle 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. Inward 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 more positive with both methodologies (P < 0.05) and was not different from zero. Further, RT-PCR showed that OX administration significantly increased mRNA concentrations of skeletal muscle AR without changing insulin-like growth factor I mRNA concentrations. We conclude that short term OX administration stimulated an increase in skeletal muscle protein synthesis and improved intracellular reutilization of amino acids. The mechanism for this stimulation may be related to an OX-induced increase in AR expression in skeletal muscle.




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