Muscle hypertrophy is the product of increased drive through protein synthetic 
pathways and the incorporation of newly divided satellite cells. Gains in muscle 
mass and strength can be achieved through exercise regimens that include 
resistance training. Increased insulin-like growth factor-I (IGF-I) can also 
promote hypertrophy through increased protein synthesis and satellite cell 
proliferation. However, it is not known whether the combined effect of IGF-I and 
resistance training results in an additive hypertrophic response. Therefore, 
rats in which viral administration of IGF-I was directed to one limb were 
subjected to ladder climbing to test the interaction of each intervention on 
muscle mass and strength. After 8 wk of resistance training, a 23.3% increase in 
muscle mass and a 14.4% increase in peak tetanic tension (P(o)) were observed in 
the flexor hallucis longus (FHL). Viral expression of IGF-I without resistance 
training produced a 14.8% increase in mass and a 16.6% increase in P(o) in the 
FHL. The combined interventions produced a 31.8% increase in muscle mass and a 
28.3% increase in P(o) in the FHL. Therefore, the combination of resistance 
training and overexpression of IGF-I induced greater hypertrophy than either 
treatment alone. The effect of increased IGF-I expression on the loss of muscle 
mass associated with detraining was also addressed. FHL muscles treated with 
IGF-I lost only 4.8% after detraining, whereas the untreated FHL lost 8.3% 
muscle mass. These results suggest that a combination of resistance training and 
overexpression of IGF-I could be an effective measure for attenuating the loss 
of training-induced adaptations.