MODULATION OF IGF MESSENGER-RNA ABUNDANCE DURING MUSCLE DENERVATION ATROPHY

Changes in skeletal muscle activity cause dramatic alterations in musc le mass. Increased load on a muscle (synergistic overload) results in muscle hypertrophy. During hypertrophy, skeletal muscle concentrations of insulin-like growth factors (IGF-I and IGF-II) mRNAs increase. To clarify the role of IGFs in regulating muscle mass, this study examine d whether IGF-I and -II mRNA levels were altered during decreased musc le activity (denervation). Gastrocnemius weights decreased 4.2%, 7.7%, 18.1%, 27.7%, 35.1%, 45.0%, and 60.3% at 2, 3, 5, 7, 10, 12, and 17 d following denervation, respectively. Muscle DNA content remained cons tant throughout the first 12 d after surgery, but increased above cont rol levels at day 17. During the first week after surgery, gastrocnemi us IGF-II mRNA remained constant. However, IGF-II mRNA abundance was 2 .5-fold greater than controls by 10 d of denervation, 3-fold by 12 d, and 6.8-fold by 17 d. On the other hand, IGF-I mRNA levels were not af fected by denervation. In conclusion, although increased muscle activi ty results in a change of IGF-I mRNA expression, decreased muscle acti vity has no effect on IGF-I mRNA expression. In contrast, IGF-II mRNA levels increase with long-term denervation as well as with increased m uscle activity. This study suggests that muscle activity may not be th e only factor affecting IGF-I and -II expression.