The growth factor myostatin (GDF-8) is a key regulator of skeletal muscle homeostasis

Physical activity and administration of anabolic steroids result in an increase of skeletal muscle mass. The molecular mechanisms involved in this adaptation are only barely characterized. Recently, the growth factor Myostatin (MSTN), a member of the TGF-ß family, has been characterized as a potent negative regulator of skeletal muscle growth and inhibitor of myoblast proliferation during embryogenesis. In this study we investigated the function of MSTN in the regulation of skeletal muscle mass in adult animals. We therefore analyzed the effect of a brief endurance training on the MSTN mRNA steady-state levels in skeletal muscle. 12-week-old male Wistar rats were divided into a training and a control group. Trained rats swam 2h/day, for 1, 3 or 5 days. 7h respectively 24h post exercise rats were sacrificed. MSTN mRNA expression in gastrocnemius and vastus lateralis muscles was determined by real time RT-PCR analysis. We found a time dependent modulation of MSTN mRNA expression in gastrocnemius muscle of trained animals. MSTN expression was transiently reduced 7h after one bout of exercise and recovered after 24h. 3 and 5-day endurance training resulted in a permanent reduction of MSTN mRNA expression in both muscles. However, the effects were lower in vastus lateralis muscle. Immunohistochemical analysis demonstrated highest myostatin expression in the region of the myotendinous junction. In summary, our data exhibit a time dependent down-regulation of the myostatin mRNA contents. The reduced MSTN mRNA levels in the trained groups demonstrate that regulation of MSTN expression is a relevant mechanism not only during the development of the muscle in the prenatal phase. Our results implicate that MSTN also play an important role in the adaptation process of skeletal muscle. Moreover, the lower muscle mRNA contents of MSTN observed in the trained animals provide evidence for a possible protective role of exercise in pathological situations like muscle dystrophy, taking into account that MSTN has been considered as a negative regulator of skeletal muscle growth.