Response of the IGF-I system to prolonged undernutrition and its involvement in somatic and skeletal muscle growth retardation in rats

We examined the response of the IGF-I system to prolonged undernutrition and its involvement in somatic and skeletal muscle growth retardation. Male rats were food-restricted to 50% of freely-fed controls (C) from birth to 120 days postpartum. Serum and tissues were collected at d 50 and d 120 postpartum. Somatic growth of food-restricted animals (R) was proportional to food intake while organ and tissue growth was disproportionate. Skeletal muscle DNA content and synthesis rates were depressed by undernutrition and DNA synthesis decreased with age. Food-restriction abated serum IGF-I concentrations, serum IGFBP-3 expression and hepatic IGF-I mRNA levels at d 50. Conversely, at d 120, hepatic IGF-I mRNA levels in R were similar to C despite decreased serum IGF-I concentrations and serum IGFBP-3 expression. Hepatic IGFBP-1 and -2 mRNA expression in R was increased at both d 50 and 120, and hepatic IGFBP-4 mRNA expression was elevated on d 120 compared to C. Gastrocnemius IGF-I mRNA levels in R were not different from C at either d 50 or 120. These results suggest that hepatic IGF-I sensitivity to undernutrition decreases with increasing age, and endocrine regulation of IGF-I following adaptation to chronic undernutrition occurs post-transcriptionally. Further, local production of IGF-I in skeletal muscle does not appear to be responsible for the marked decline in muscle DNA synthesis, for skeletal muscle IGF-I mRNA expression was not altered by undernutrition.