EFFECT OF HUMAN GROWTH-HORMONE AND INSULIN-LIKE GROWTH FACTOR-I ON WHOLE-BODY LEUCINE AND ESTIMATES OF PROTEIN-METABOLISM

Recombinant human growth hormone (rhGH) administration to normal volun teers increases estimates of whole-body and forearm protein synthesis but has little effect on rates of proteolysis in both the postabsorpti ve state and during meal absorption. In contrast, insulin decreases es timates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimate s of protein synthesis. We have used high-dose prednisone as a control led model for protein catabolism in normal volunteers and demonstrated that glucocorticosteroids increase estimates of whole-body proteolysi s and the oxidation of leucine with little or no effect on estimates o f whole-body protein synthesis. We have recently demonstrated that hig h-dose rhGH together with prednisone prevents the protein-catabolic ef fects observed with treatment with prednisone alone, while inducing in sulin resistance and increased secretion of proinsulin. GH is thought to mediate its effects via the generation of insulin-like growth facto r I (IGF-I). However, high rates of infusion of rhIGF-I induce hypogly cemia and decrease estimates of whole-body proteolysis and suppress th e secretion of GH, insulin and glucagon, suggesting a predominant insu lin-like effect on protein and glucose metabolism. When rhIGF-I is inf used at a rate that achieves plasma IGF-I concentrations similar to th ose observed during rhGH treatment and yet avoids hypoglycemia, estima tes of proteolysis and protein synthesis were not affected in the abse nce or presence of prednisone treatment.When rhGH and rhIGF-I are admi nistered simultaneously, nitrogen balance is remarkably improved. Thus , the mechanism of action of both rhGH and/or rhIGF-I on body protein metabolism remains to be elucidated. However, rhGH alone or in combina tion with rhIGF-I may provide a new management strategy in a variety o f protein-catabolic conditions in humans.