Attenuation by nandrolone of chronic but not acute denervation atrophy.

Denervation results in loss of skeletal muscle associated with increased expression of MAFbx and MuRF1. Objectives: Test the effect of nandrolone (an anabolic steroid) on atrophy due to denervation; to test whether such effects are linked to reduced expression of muscle degradation factors (MAFbx, MuRF1) or increased IGF-1. Methods: Male Wistar rats underwent left sciatic nerve transection and right sham transection. At that time, or 28 days later, animals were administered nandrolone (0.75 mg/kg/wk) or vehicle. 3 to 28 days later, muscles were weighed, and gene expression was determined. Results: Denervation caused severe atrophy of gastrocnemius muscle (88% after 56 days). When drug therapy was begun 28 days after denervation, denervated gastrocnemius was 15% larger in nandrolone animals 7 or 28 days of treatment (days 35 or 56 post-denervation). This effect was associated with significant reductions in expression of MAFbx, MuRF1 but not IGF-1 or its binding proteins. When nandrolone was begun at the time of denervation, no effect on atrophy or gene expression was observed over the first 14 days after nerve transection. Conclusions: The severe atrophy associated with denervation can be reduced by nandrolone. Response of muscle to nandrolone depends on time after denervation suggesting evolution over the first 28 days after denervation of the “program” of muscle atrophy from one that is nandrolone-resistant to one that is nandrolone-sensitive. Funded by the Department of Veterans Affairs RR&D Service.