Short- and Long-Term Effects of Growth Hormone (GH) Replacement on Protein Metabolism in GH-Deficient Adults

Reduced fat-free mass (FFM) in GH-deficient (GHD) adults is improved by GH replacement, but the protein metabolic changes are unclear. Using iv [ ²H₃]leucine and oral 1-[¹³C₁] leucine infusions and dual emission x-ray absorptiometry, we compared leucine kinetics and body composition in eight GHD adults and eight healthy controls in the fasted and fed states, before and after 2 wk and 6 months of GH replacement. Leucine kinetics were not different between pretreatment GHD subjects and controls. After 2 wk of GH treatment, leucine oxidation decreased in the GHD subjects compared with baseline values [fasted, 41 ± 6 vs. 30 ± 5 μmol/kg FFM·h (P < 0.01); fed, 49 ± 3 vs. 41 ± 3.6 μmol/kg FFM·h (P < 0.05)], leucine balance improved [fasted, -14 ± 4 vs. -3.5 ± 3 μmol/kg FFM·h (P < 0.01); fed, 65 ± 10 vs. 72 ± 7 μmol/kg FFM·h (P = 0.07)], and protein synthesis increased [fasted, 116 ± 5 vs. 131 ± 6 μmol/kg FFM·h (P < 0.05); fed, 103 ± 6 vs. 116 ± 6 μmol/kg FFM·h (P < 0.05)]. After 6 months of GH treatment, these changes were not maintained in the fed state. The five GHD subjects with decreased FFM at baseline showed a significant increase after 6 months of GH treatment (P < 0.05). GH replacement in GHD acutely improves protein balance by stimulating synthesis and inhibiting catabolism. After 6 months, protein kinetics reached a new homeostasis to maintain the net gain in FFM.