Ghrelin in the Regulation of GH Secretion and Other Pituitary Hormones

Abstract

Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) exert profound effects on energy, lipid, protein, and carbohydrate metabolism. GH increases energy expenditure, lipolysis, and lipid oxidation, actions that account for the reduc-tion in fat mass during GH replacement. The increase in lean body and skeletal muscle mass induced by GH is mediated by an increase in protein synthesis and a reduction in irreversible oxidative loss of amino acids. While GH excess causes insulin resis-tance, the effect of lower doses of GH on carbohydrate metabolism is variable and dependent on changes in lipolysis, abdominal adiposity, and IGF-1. IGF-1 augments some of the metabolic effects of GH, but counteracts others. Like GH, IGF-1 increases protein mass by reducing protein oxidation and increas-ing protein synthesis. However, IGF-1 has an insulin-like effect on carbohydrate metabolism that partially offsets the effect of GH excess. The effect of IGF-1 on lipid metabolism is likely to be indirectly mediated by changes in GH and insulin secretion. Finally, there is not a single effect of GH and IGF-1 on lipid, protein, and carbo-hydrate metabolism. Rather, there is a spectrum of effects determined by dose, dura-tion of use, and underlying disease state. Integration of many variables is needed to explain the metabolic actions of GH and IGF-1 in acromegaly and GH deficiency and the effect of GH replacement in the latter.