Regulation of insulin-like growth factor 1 gene expression in skeletal muscle.

Insulin-like growth factor 1 (IGF-1) is implicated in the growth processes of many tissues in the adult animal. This hormone can act in an endocrine manner or can be produced in the specific tissues in response to growth promoting stimuli to act in an autocrine/paracrine manner. We have examined, in the rat, changes in serum concentrations of IGF-1 and muscle IGF-1 mRNA levels in several studies in which muscle growth has been significantly altered. In the first study we examined the interactions of growth hormone (GH) and under-nutrition upon muscle growth. We observed that when GH was administered to hypophysectomised rats the anabolic effect of this hormone was independent of dietary intake. In a similar manner muscle IGF-1 mRNA levels were also elevated by GH but unaffected by food intake. In contrast serum IGF-1 levels were markedly reduced by under-nutrition. These data suggested that the anabolic action of GH on muscle could be mediated through the autocrine/paracrine action of the IGF-1 hormone. Similarly we observed in other studies that muscle hypertrophic stimuli of work-overload and passive stretch are associated with significantly increased muscle IGF-1 mRNA levels. In contrast insulin dramatically affected muscle protein synthesis rates but had no measurable effect upon muscle IGF-1 mRNA levels, which suggests that the anabolic action of this hormone is not mediated through the autocrine/paracrine action of IGF-1. These studies suggest that IGF-1 may mediate growth in muscle in response to variety of stimuli by autocrine/paracrine action or in response to certain stimuli possibly by endocrine action.