ARE THE METABOLIC EFFECTS OF GH AND IGF-I SEPARABLE?

Authors: MAURAS, NELLY - NEMOURS CHILDREN'S CLINIC; Haymond, Morey

Submitted to: Growth Hormone and IGF Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/15/2004
Publication Date: 2/15/2005
Citation: Mauras, N., Haymond, M.W. 2005. Are the metabolic effects of GH and IGF-I separable? Growth Hormone and IGF Research. 15(1):19-27.

Interpretive Summary: Insulin-like growth factor 1 (IGF-I) mediates some, but not all of the metabolic actions of human growth hormone (GH). It has been known for some time that IGF-I has both GH-like and insulin-like actions in vivo. GH and IGF-I both have been demonstrated to enhance whole body protein synthesis over a period of weeks and perhaps months. Both hormones favorably improve body composition in GH deficient subjects by increasing lean body mass and decreasing fat mass. This is also observed when IGF-I is given to patients with GH-receptor mutations which interferes with GH binding to the receptor. However GH and IGF-1 have divergent effects on carbohydrate metabolism. IGF-I administration leads to a lowering of plasma glucose and improved insulin sensitivity in the face of a marked lowering of circulating insulin concentrations, whereas GH therapy is associated increased plasma insulin concentrations, a reflection of relative insulin resistance. The latter observation makes IGF-I a potentially more convenient anabolic agent to use in conditions where carbohydrate metabolism is more likely to be impaired. GH increases fat mobilization as a direct effect of GH on the fat cell, as well as fat oxidation by increasing fatty acid availability. However IGF-I increases lipid oxidation only when given chronically, most likely as a result of the chronic lower insulin concentrations. These compounds are used in a variety of catabolic conditions in man. Both hormones have been effective in reducing the protein wasting effects of steroids (glucocorticosteroids) and decrease some of the protein loss in men with very low plasma testosterone. A comparison of these and other effects of these two hormones is provided in this brief review. Subsequent studies are still needed to fully elucidate the safety and efficacy of IGF-I for use in humans.

Technical Abstract: IGF-I mediates some, but not all of the metabolic actions of GH and it has both GH-like and insulin-like actions in vivo. GH and IGF-I both have a net anabolic effect in man enhancing whole body protein synthesis over a period of weeks and perhaps months. Both hormones favorably improve body composition in GH deficient subjects with an increase in lean body mass and decreased adiposity. This is also observed when IGF-I is given to patients with GH-receptor mutations. These compounds, however, have divergent effects on carbohydrate metabolism. A potent glucose lowering effect is typically observed after IGF-I administration, with improved insulin sensitivity with marked lowering of circulating insulin concentrations, whereas GH therapy is associated with mild compensatory hyperinsulinemia, a reflection of relative insulin resistance. The latter observation makes IGF-I a potentially more convenient anabolic agent to use in conditions where carbohydrate metabolism is more likely to be impaired. GH increases lipolysis as a direct effect of GH on the adipocyte, as well as lipid oxidation by increasing substrate availability. However IGF-I increases lipid oxidation only when given chronically, most likely as a result of chronic insulinopenia. These compounds have been tried in a variety of catabolic conditions in man and both hormones have been effective in reducing the protein wasting effects of glucocorticosteroids and mitigate some of the catabolic effects of severe hypogonadism in males. A comparison of these and other effects of these hormones is provided in this brief review. Subsequent studies are still needed to fully elucidate the safety and efficacy of IGF-I for use in humans.