REDUCED SERUM CONCENTRATIONS OF INSULIN-LIKE GROWTH FACTOR-I (IGF-I) IN PROTEIN-RESTRICTED GROWING RATS ARE ACCOMPANIED BY REDUCED IGF-I MESSENGER-RNA LEVELS IN LIVER AND SKELETAL-MUSCLE

The serum concentration of insulin-like growth factor-I (IGF-I) is reduced in growing rats fed a low-protein diet, and this decrease is age-dependent, being more pronounced in younger animals. To determine whether this decrease in serum IGF-I is related to a decrease in IGF-I mRNA, growing female rats were given free access to either a 15% protein-sufficient or a 5% protein-deficient diet for 1 week. Protein restriction in 4-week-old rats decreased body weight gain by 44% (P < 0.001 compared with 4-week controls), serum IGF-I concentration by 67% (P < 0.001) and liver IGF-I mRNA abundance by 51% (P < 0.001). During week 6, protein restriction for 1 week resulted in a 20% increase in food intake with no change in weight gain, a 38% reduction in serum IGF-I (P < 0.001 compared with 6-week controls) and a 39% decrease in liver IGF-I mRNA (P < 0.001). The serum IGF-I concentration was highly correlated (r = 0.80; P < 0.001) with the hepatic IGF-I mRNA concentration. Skeletal muscle IGF-I mRNA abundance was also decreased significantly by protein restriction (37% at week 4, P < 0.001, and 24% at week 6, P < 0.01) and was closely correlated (r = 0.71; P < 0.001) with body weight gain. Liver GH-binding protein and GH receptor mRNA abundance were reduced by 1 week of protein deprivation at week 6 but not at week 4. We conclude that the reduced serum IGF-I of young rats fed a low-protein diet is due, in part, to reduced liver IGF-I mRNA, and that these changes are not dependent on GH binding. Decreased skeletal muscle IGF-I mRNA during protein restriction is consistent with an autocrine/paracrine action of IGF-I in muscle.