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Skeletal muscle adaptations to testosterone and resistance training in men with COPD

Divisions of ¹Pulmonary and Critical Care Medicine and of ²Endocrinology, Diabetes, and Metabolism, The Burns and Allen Research Institute at Cedars-Sinai Medical Center, Los Angeles; ³David Geffen School of Medicine at UCLA, Los Angeles; ⁴Exercise Sciences Laboratory, El Camino College, Torrance; ⁵Division of Endocrinology, Metabolism, and Molecular Medicine, Drew University of Medicine and Science, Los Angeles; and ⁶Division of Respiratory and Critical Care Physiology and Medicine, Rehabilitation Clinical Trials Center, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California

Submitted 5 February 2007 ; accepted in final form 20 July 2007

We recently reported increased leg lean mass and strength in men with chronic obstructive pulmonary disease (COPD) receiving 10 wk of testosterone (T) and leg resistance training (R) (Casaburi R, Bhasin S, Cosentino L, Porszasz J, Somfay A, Lewis M, Fournier M, Storer T. Am J Respir Crit Care Med 170: 870–878, 2004). The present study evaluates the role of muscle IGF and related factors as potential mechanisms for our findings, using quadriceps muscle biopsies from the same cohort. Patient groups were 1) weekly placebo (P) injections + no R; 2) P and R; 3) weekly injections of T + no R; and 4) T + R (TR). Muscle fibers were classified histochemically, and their cross-sectional areas (CSAs) and fiber density (number of fibers per unit area) were determined. Gene transcripts were determined by real-time PCR and protein expression by RIA. While no significant changes in fiber CSAs were noted across groups, increased trends were observed after 10 wk, and significant decrements in muscle fiber density were noted in all treated groups. A global increase in all myosin heavy chain (MyHC) mRNA isoforms was observed in TR patients. Muscle IGF-IEa and IGF-IEc mRNAs were significantly increased with TR group. Muscle IGF-I protein was increased in all intervention groups (greatest in TR). While TR IGF-II mRNA was increased, protein levels were unaltered. IGF binding protein-4 mRNA was increased with TR. Myogenin mRNA was increased in both T groups, while MyoD and myostatin were unchanged. Muscle atrophy F-box mRNA tended to increase with TR. Our data suggest that the combined interventions produced an enhanced local anabolic milieu driven in large part by the muscle IGF system, despite potentially negative biochemical influences present in COPD patients.

anabolic steroids; emphysema; vastus lateralis; insulin-like growth factors; myogenic regulatory factors; myosin heavy chains; muscle fiber morphometry