MODULATION OF THE INSULIN-LIKE-GROWTH-FACTOR SYSTEM BY CHRONIC ALCOHOL FEEDING

Insulin-like growth factor (IGF)-I is a potent anabolic agent that pla ys an important role in regulating muscle protein balance. Alterations in one or more of the various components of the IGF system may be in part responsible for the muscle wasting that accompanies chronic alcoh ol consumption. The purpose of the present study was to characterize c hanges in the growth hormone-IGF axis produced by chronic alcohol cons umption in rats. After 8 weeks of alcohol feeding, the IGF-I concentra tion was decreased in plasma (31%) as well as in the liver and skeleta l muscle (40-50%), compared with pair-fed control animals. In addition , alcohol consumption decreased IGF-I mRNA abundance in liver and musc le (similar to 50%). IGF-I content in duodenum and kidney, however, wa s not altered by alcohol feeding. Concomitantly, the relative concentr ation of IGF binding protein (IGFBP)-1 was increased in plasma, liver, and muscle of alcohol-fed rats, compared with control values. In cont rast, no changes in the plasma concentrations of IGFBP-2, -3, or -4 we re detected in alcohol-fed rats at this time point. Previous studies h ave indicated that elevations in glucocorticoids or decreases in insul in or growth hormone might be responsible for the decrease in IGF-I an d/or the increase in IGFBP-1 in other catabolic conditions. However, t here was no difference in the plasma concentrations of these hormones between alcohol-fed and control animals in this study. These data indi cate that chronic alcohol feeding in rats decreases IGF-I and increase s IGFBP-1 in the circulation and in skeletal muscle and that these cha nges appear to be independent of changes in classical hormonal regulat ors of the IGF system. The observed alterations in the IGF system are consistent with a reduction in the anabolic actions of IGF-I induced b y chronic alcohol consumption.