Metabolic Effects of Growth Hormone on Protein and Lipids

Abstract

The development of techniques for large scale production of human growth hormone (GH) and insulin like growth factor-I (IGF-I) by recombinant deoxyribonucleic acid (DNA) technology has led to a resurgence in interest in their metabolic actions and clinical applications. The metabolic actions of GH can be divided into direct effects on carbohydrate, fat and protein, and indirect actions mediated primarily through IGF-I and insulin. IGF-I and insulin increase in response to GH treatment and the metabolic effects on carbohydrate, fat and protein of each are similar but not identical. Although the primary regulator of IGF-I is GH, nutritional effects on IGF-I may predominate during conditions of extreme undernutrition or overnutrition. Obesity is associated with impaired GH secretion, and total IGF-I concentrations in blood are reduced, assuming energy balance is maintained. GH treatment is associated with reduced percent body fat and increased lean body mass, although treatment of obesity with GH has been relatively ineffective, if combined with nutrient restriction.The direct effects of GH on glucose and fat metabolism are intimately related. GH-stimulated lipolysis leads to release of free fatty acids and inhibition of insulin-stimulated glucose uptake by skeletal muscle. This effect, combined with stimulation of glycogenolysis and gluconeogenesis, leads to hyperglycemia. The principal protein metabolic action of GH is a rapid reduction in amino acid oxidation. Within hours of exposure to GH, whole body protein synthesis (WBPS) increases, followed by an increase in the rate of skeletal muscle protein synthesis. This effect is associated with an increase in blood flow to muscle tissue, likely mediated by IGF-I and/or insulin. In summary, the effects of GH on body composition reflect a complex interaction between GH and its metabolic fuels in the short term, and the metabolic actions of IGF-I and insulin on carbohydrate, fat, and protein subsequently.