Growth hormone and insulin-like growth factor-I therapy promote protein deposition and growth in dexamethasone-treated piglets

Background: Dexamethasone treatment facilitates the weaning of premature in fants from mechanical ventilation but impairs protein homeostasis, lean tis sue 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 +/- ins ulin-like growth factor-I therapy can attenuate such effects. Methods: Piglets (n = 24) were randomized to placebo, a tapered course of d examethasone (0.5, 0.3, 0.2 mg/kg per day for 5, 5 and 4 days each, respect ively), 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 da ys. On day 13, N-15-glycine was administered as a single oral dose, and uri ne was collected at timed intervals during the subsequent 48 hours. Results: Total urinary N and cumulative N-15 excretion were higher in all d examethasone groups than in control subjects. Protein synthesis was suppres sed, whereas protein breakdown was unaltered by dexamethasone. Adjunctive g rowth hormone +/- insulin-like growth factor-I therapy enhanced protein syn thesis, but only combined therapy improved net protein gain compared with d examethasone alone. Higher circulating insulinlike 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 da y 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-in duced reduction in weight and length gain but not in whole body lean and fa t mass. Conclusion: Adjunctive growth hormone +/- insulin-like growth factor-I ther apy partially reverses the dexamethasone-induced reduction in protein synth esis, resulting in improved growth when given concurrently with a low taper ing dose of dexamethasone.