Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/1/2003
Publication Date: 12/1/2003
Citation: SHI, J., SEKHAR, R.V., BALASUBRAMANYAM, A., ELLIS, K.J., REEDS, P.J., JAHOOR, F., SHARMA, M.D. 2003. SHORT- AND LONG-TERM EFFECTS OF GROWTH HORMONE REPLACEMENT ON PROTEIN METABOLISM IN GROWTH HORMONE DEFICIENT ADULTS. JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. 88(12):5827-5833. Interpretive Summary: Adults with acquired growth hormone deficiency (GHD) generally have reduced lean and muscle tissue, but increased fat mass, when compared to weight-and age-matched healthy adults. Replacement of Growth hormone (GH) can improve the amount of muscle and lean tissue mass in GHD patients, however, the mechanism has not been clearly established. We placed GHD adults on GH treatment for 6 months, and as expected, muscle increased and fat decreased. Using special isotopes to monitor what was happening to protein in the body, we were able to show that new tissue was built up faster and older tissues were reabsorbed slower than without GH. By six months there was a balance between building up and breaking down muscle tissues, so that the subjects could maintain their increase in muscle mass. This study demonstrates that using GH may provide a mechanism for helping adults regain lost muscle or lean tissues.
Technical Abstract: Reduced fat free mass (FFM) in growth hormone deficient (GHD) adults is improved by GH replacement, but the protein metabolic changes are unclear. Using intravenous [2H3-] and oral [13C-] leucine infusions and DEXA, we compared leucine kinetics and body composition in 8 GHD adults and 8 healthy controls in the fasted and fed states, before and after 2 weeks and 6 months of GH replacement. Leucine kinetics (umol/kg FFM/h) were not different between pre-treatment GHD subjects and controls. After 2 weeks of GH, leucine oxidation decreased in the GHD subjects compared to baseline (fasted: 41±6 vs. 30±5, P < 0.01; fed: 49±3 vs. 41±3.6, P < 0.05), leucine balance improved (fasted: -14±4 vs. -3.5±3, P <0.01; fed: 65±10 vs. 72±7, P = 0.07), and protein synthesis increased (fasted: 116±5 vs. 131±6, P<0.05; fed: 103±6 vs. 116±6, P<0.05). After 6 months of GH, these changes were not maintained in the fed state. The 5 GHD subjects with decreased FFM at baseline showed a significant increase after 6 months of GH (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.