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

Division of Endocrinology, Department of Medicine, Children’s Nutrition Research Center (J.S., R.V.S., A.B., M.D.S.); Department of Pediatrics, Baylor College of Medicine (R.V.S., K.E., P.J.R., F.J.); and Ben Taub General Hospital (A.B., M.D.S.), Houston, Texas 77030

Address all correspondence and requests for reprints to: Morali D. Sharma, M.D., Division of Endocrinology, 6565 Fannin, Room B-250, Houston, Texas 77030. E-mail: msharma{at}bcm.tmc.edu.

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 l-[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.

This work was supported by an investigator-initiated research grant from Eli Lilly & Co. (to M.D.S.), a Chao Scholar Award (to A.B.), federal funds from the U.S. Department of Agriculture, Agricultural Research Service under Cooperative Agreement 58-6250-6001 (to F.J.), and NIH General Clinical Research Center Grant MO1-RR-00188. The contents of this manuscript do not necessarily reflect the views or policies of the USDA. The mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government.

J.S. and R.V.S. contributed equally to this work.

Abbreviations: BMI, Body mass index; FFM, fat-free mass; FM, fat mass; GHD, GH deficient; KICA, -ketoisocaproic acid.

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