A DOSE-RESPONSE STUDY OF GROWTH-HORMONE (GH) REPLACEMENT ON WHOLE-BODY PROTEIN AND LIPID KINETICS IN GH-DEFICIENT ADULTS

This study was designed to establish the lower dose of effective GH re placement therapy in severe GK-deficient (GHD) adults. Whole body prot ein and lipid kinetics were determined in six GHD men in the basal sta te (B) and after 1 week of treatment with placebo (PL) or 3.3 (GH3.3) or 2 (GH2) mu g/kg.day recombinant human GH (rhGH). The rates of whole body proteolysis, oxidation, and synthesis were estimated by infusing [1-C-13]leucine (prime, 1 mg/kg; infusion rate, 1 mg/kg.h); those of lipolysis (measured in four of the six patients) were estimated by inf using [1,1,2,3,3-D-5]glycerol (prime, 1.8 mu mol/kg; infusion rate, 0. 06 mu mol/kg.min). Serum insulin-like growth factor I (IGF-I) concentr ations (picograms per mL; mean +/- SE) similarly increased from the ba sal level (39 +/- 7) after 3.3 (108 +/- 18) or 2 (109 +/- 24) mu g/kg day rhGH (P < 0.001 vs. basal), whereas they did not change with place bo (41 +/- 8). Leucine Ra was unaffected by the treatments. GH3.3 redu ced by 30% the rate of leucine oxidation (P = 0.0069 vs. basal) and in creased by 11% nonoxidative leucine disposal (P = 0.0095 vs. basal) an d by 21% glycerol Ra (0.0035 vs. basal); GH2 and placebo had no signif icant effect. In conclusion, 1) at least 3.3 mu g/kg.day rhGH are requ ired to increase whole body protein synthesis and lipolysis in male GH D adults; 2) 2 mu g/kg.day rhGH normalize serum IGF-I concentrations, but do not modify protein and lipid metabolism; and 3) a normal serum IGF-I concentration does not guarantee that rhGH treatment is also eff ective on intermediate metabolism.