EFFECTS OF INSULIN-LIKE-GROWTH-FACTOR-I COMBINED WITH GROWTH-HORMONE ON GLUCOCORTICOID-INDUCED WHOLE-BODY PROTEIN CATABOLISM IN MAN

Treatment with insulin-like growth factor I(IGF-I) alone failed to aff ect glucocorticoid-induced protein catabolism in a precious study from our laboratory. To assess the effects of the combination of IGF-I and GH in a similar protocol, 24 normal subjects received (in a double-bl ind. randomized, placebo-controlled manner) sc injections of either GH alone (0.3 IU/kg.day), the combination of IGF-I(80 mu g/kg.day) and G H (0.3 IU/kg.day), or placebo for a period of 6 days during which they were treated with methylprednisolone (0.5 mg/kg.day). Whole-body prot ein kinetics measured, using the [1-C-13]-leucine infusion technique, demonstrated that leucine flux (a parameter of protein breakdown incre ased during administration of glucocorticoids alone (placebo group! an d during GH-treatment, whereas the glucocorticoid-induced increase was abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation ( a parameter of irreversible protein catabolism) increased in the place bo group (+60 +/- 14.5%, P < 0.005, day 7 cs. day 1), remained unchang ed in the GH group (+2.5 +/- 10%), and decreased in the combination gr oup (-17.7 +/- 3.3%, P < 0.002, day 7 cs. day 1). Glucose MCR decrease d in the group receiving placebo (P < 0.05) and remained unchanged dur ing combined treatment with IGF-I plus GH. It is concluded that glucoc orticoid-induced protein catabolism (leucine oxidation) is abolished d uring coadministration of GH (anticatabolic effect), whereas treatment with IGF-I and GH results in a net anabolic effect without adverse ef fects on peripheral glucose clearance.