Metabolic actions of growth hormone: Direct and indirect

GH may exert metabolic effects either directly or indirectly through increased production of IGF-I. GH administration increases circulating IGF-I levels via stimulation of hepatic synthesis and secretion of IGF-I; it may also enhance local IGF-I synthesis, which exerts paracrine or autocrine effects. Figure 2 summarizes the metabolic effects of GH and IGF-I. Administration of GH and IGF-I in adult humans has been demonstrated to enhance protein anabolism. Combined administration of GH and IGF-I was observed to be more anabolic than either IGF-I or GH alone. Evidence is presented that protein accretion results mainly from direct effects of GH on tissues; additional indirect effects via IGF-I production are also likely. Administration of GH has been reported to produce carbohydrate intolerance with elevated plasma insulin levels, resulting from insulin resistance. In contrast, insulin sensitivity increased during administration of IGF-I, which exerts hypoglycaemic effects even with concomitant suppression of insulin secretion. A major direct metabolic effect of GH is to increase fat mobilization and oxidation, and thereby to reduce total body fat; there is no evidence that IGF-I acts directly on adipose tissue in vivo. GH administration results in sodium retention via stimulation of Na-K-ATPase. It is suggested that part of the effects of GH on tubular function (e.g. phosphate reabsorption) are mediated via IGF-I. Energy expenditure may be increased by administration of either GH or relatively high doses of IGF-I. One of the reasons for this phenomenon is an increase in lean body mass; GH may increase energy expenditure additionally by enhancing the production of T, and by increasing lipid oxidation.