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 [(2)H(3)]leucine and oral l-[(13)C(1)]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 micromol/kg FFM.h (P < 0.01); fed, 49 +/- 3 vs. 41 +/- 3.6 micromol/kg FFM.h (P < 0.05)], leucine balance improved [fasted, -14 +/- 4 vs. -3.5 +/- 3 micromol/kg FFM.h (P < 0.01); fed, 65 +/- 10 vs. 72 +/- 7 micromol/kg FFM.h (P = 0.07)], and protein synthesis increased [fasted, 116 +/- 5 vs. 131 +/- 6 micromol/kg FFM.h (P < 0.05); fed, 103 +/- 6 vs. 116 +/- 6 micromol/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.
Shi
Jianjian
J
Department of Medicine, Children's Nutrition Research Center, Baylor College of Medicine, Houston, Texas 77030, USA.
Sekhar
Rajagopal V
RV
Balasubramanyam
Ashok
A
Ellis
Kenneth
K
Reeds
Peter J
PJ
Jahoor
Farook
F
Sharma
Morali D
MD
D000328:Adult; D000368:Aged; D001823:Body Composition / Q000187:drug effects; D016022:Case-Control Studies; D005215:Fasting / Q000378:metabolism; D005260:Female; D006706:Homeostasis; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D007930:Leucine / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000378:metabolism; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D013997:Time Factors
D019382:Human Growth Hormone; D007930:Leucine