Submitted on February 5, 2007
Accepted on July 20, 2007
Skeletal Muscle Adaptations to Testosterone and Resistance Training in Men with COPD
Michael I. Lewis1*, Mario Fournier1, Thomas W. Storer2, Shalender Bhasin3, Janos Porszasz4, Song-Guang Ren5, Xiaoyu Da6, and Richard Casaburi7
1 Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center, United States; Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
2 Exercise Sciences Laboratory, El Camino College, Torrance, California, United States
3 Division of Endocrinology, Metabolism, and Molecular Medicine, Drew University of Medicine and Science, Los Angeles, California, United States; Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
4 Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States
5 Division of Endocrinology, Diabetes, and Metabolism, Cedars-Sinai Medical Center, Los Angeles, California, United States
6 Division of Pulmonary/Critical Care Medicine, Cedars-Sinai Medical Center, United States
7 Division of Respiratory and Critical Care Physiology and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California, United States; Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, United States
* To whom correspondence should be addressed. E-mail: michael.lewis{at}cshs.org.
We recently reported increased leg lean mass and strength in men with COPD receiving 10 weeks of testosterone (T) and leg resistance training (R). This 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) 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 weeks, and significant decrements in muscle fiber density 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. 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.
