Recombinant human growth hormone (rhGH) administration to normal volunteers increases estimates of whole-body and forearm protein synthesis but has little effect on rates of proteolysis in both the postabsorptive state and during meal absorption. In contrast, insulin decreases estimates of whole-body and forearm proteolysis while decreasing or, in the presence of infused (or ingested) amino acids, sustaining estimates of protein synthesis. We have used high-dose prednisone as a controlled model for protein catabolism in normal volunteers and demonstrated that glucocorticosteroids increase estimates of whole-body proteolysis and the oxidation of leucine with little or no effect on estimates of whole-body protein synthesis. We have recently demonstrated that high-dose rhGH together with prednisone prevents the protein-catabolic effects observed with treatment with prednisone alone, while inducing insulin resistance and increased secretion of proinsulin. GH is thought to mediate its effects via the generation of insulin-like growth factor I (IGF-I). However, high rates of infusion of rhIGF-I induce hypoglycemia and decrease estimates of whole-body proteolysis and suppress the secretion of GH, insulin and glucagon, suggesting a predominant insulin-like effect on protein and glucose metabolism. When rhIGF-I is infused at a rate that achieves plasma IGF-I concentrations similar to those observed during rhGH treatment and yet avoids hypoglycemia, estimates of proteolysis and protein synthesis were not affected in the absence or presence of prednisone treatment. When rhGH and rhIGF-I are administered 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.(ABSTRACT TRUNCATED AT 250 WORDS)