Regulation of IGF-I Activity by Protein Nutrition.

Insulin-like growth factor-I (IGF-I) is an important growth factor for postnatal growth, and its plasma concentration is known to be regulated by nutrition. To investigate the mechanisms of regulation of IGF-I activity by IGF-I receptor (IGF-IR) and IGF-binding protein (IGFBP) under various nutritional conditions, the mRNA content and protein level of IGF-IR and IGFBP were studied with rats fed diets containing low amounts or a low nutritional quality of protein. The IGF-IR mRNA level and IGF binding activity in various tissues of the rats were not affected by dietary protein malnutrition. Among IGFBP-1-4, which are thought to be the main IGFBPs in plasma, the plasma IGFBP-1 concentration showed the greatest increase in response to dietary protein deprivation. The increased plasma IGFBP-1 level was accompanied by an increase in both liver mRNA content and the rate of transcription of its gene. Transient transfection analysis of deletion mutants demonstrated that the sequence -112--81 by 5′ to the transcription start site was responsible for the induction of IGFBP-1 gene transcription by dietary protein deprivation.

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