Dexamethasone inhibits the stimulation of muscle protein synthesis and PHAS-I and p70 S6-kinase phosphorylation.

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Abstract
Glucocorticoids inhibit protein synthesis in muscle. In contrast, insulin and amino acids exert anabolic actions that arise in part from their ability to phosphorylate ribosomal p70 S6-kinase (p70S6k) and eukaryotic initiation factor (eIF)4E binding protein (BP)1 (PHAS-I), proteins that regulate translation initiation. Whether glucocorticoids interfere with this action was examined by giving rats either dexamethasone (DEX, 300 μg · kg−1 · day−1, n = 10) or saline ( n = 10) for 5 days. We then measured the phosphorylation of PHAS-I and p70S6kin rectus muscle biopsies taken before and at the end of a 180-min infusion of either insulin (10 mU · min−1 · kg−1 euglycemic insulin clamp, n = 5 for both DEX- and saline-treated groups) or a balanced amino acid mixture ( n = 5 for each group also). Protein synthesis was also measured during the infusion period. The results were that DEX-treated rats had higher fasting insulin, slower glucose disposal, less lean body mass, and decreased protein synthetic rates during insulin or amino acid infusion ( P < 0.05 each). DEX did not affect basal PHAS-I or p70S6k phosphorylation but blocked insulin-stimulated phosphorylation of PHAS-I- and amino acid-stimulated phosphorylation of both PHAS-I and p70S6k ( P < 0.01, for each). DEX also increased muscle PHAS-I concentration. These effects can, in part, explain glucocorticoid-induced muscle wasting.

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