Growth Hormone and Insulin-like Growth Factor-I Therapy Promote Protein Deposition and Growth in Dexamethasone-treated Piglets
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BACKGROUND: Dexamethasone treatment facilitates the weaning of premature infants from mechanical ventilation but impairs protein homeostasis, lean tissue deposition, and growth. The current study was conducted to investigate whether dexamethasone mediates these effects by reducing protein synthesis or elevating protein breakdown, and whether adjuvant growth hormone+/-insulin-like growth factor-I therapy can attenuate such effects. METHODS: Piglets (n = 24) were randomized to placebo, a tapered course of dexamethasone (0.5, 0.3, 0.2 mg/kg per day for 5, 5 and 4 days each, respectively), dexamethasone + growth hormone 0.1 mg/kg per day, or dexamethasone + growth hormone + insulin-like growth factor-I 0.1 mg/kg per day for 14 days. On day 13, 15N-glycine was administered as a single oral dose, and urine was collected at timed intervals during the subsequent 48 hours. RESULTS: Total urinary N and cumulative 15N excretion were higher in all dexamethasone groups than in control subjects. Protein synthesis was suppressed, whereas protein breakdown was unaltered by dexamethasone. Adjunctive growth hormone+/-insulin-like growth factor-I therapy enhanced protein synthesis, but only combined therapy improved net protein gain compared with dexamethasone alone. Higher circulating insulin-like growth factor-I may have mediated the greater net protein gain. Blood urea nitrogen was elevated in all dexamethasone-treated groups at days 6 and 11 but was normalized by day 15 with adjunctive growth hormone+/-insulin-like growth factor-I. From a functional perspective, both adjunctive growth hormone and growth hormone+/-insulin-like growth factor-I partially attenuated the dexamethasone-induced reduction in weight and length gain but not in whole body lean and fat mass. CONCLUSION: Adjunctive growth hormone+/-insulin-like growth factor-I therapy partially reverses the dexamethasone-induced reduction in protein synthesis, resulting in improved growth when given concurrently with a low tapering dose of dexamethasone.