Prolonged exposure to glucocorticoids in pharmacologic amounts results in muscle wasting, but whether changes in plasma cortisol within the physiologic range affect amino acid and protein metabolism in man has not been determined. To determine whether a physiologic increase in plasma cortisol increases proteolysis and the de novo synthesis of alanine, seven normal subjects were studied on two occasions during an 8-h infusion of either hydrocortisone sodium succinate (2 μg/kg.min) or saline. The rate of appearance (Ra) of leucine and alanine were estimated using [2H3]leucine and [2H3]alanine. In addition, the Ra of leucine nitrogen and the rate of transfer of leucine nitrogen to alanine were estimated using [15N]leucine. Plasma cortisol increased (10±1 to 42±4 μg/dl) during cortisol infusion and decreased (14±2 to 10±2 μg/dl) during saline infusion. No change was observed in plasma insulin, C-peptide, or glucagon during either saline or cortisol infusion. Plasma leucine concentration increased more (P < 0.05) during cortisol infusion (120±1 to 203±21 μM) than saline (118±8 to 154±4 μM) as a result of a greater (P < 0.01) increase in its Ra during cortisol infusion (1.47±0.08 to 1.81±0.08 μmol/kg.min for cortisol vs. 1.50±0.08 to 1.57±0.09 μmol/kg.min). Leucine nitrogen Ra increased (P < 0.01) from 2.35±0.12 to 3.46±0.24 μmol/kg.min, but less so (P < 0.05) during saline infusion (2.43±0.17 to 2.84±0.15 μmol/kg.min, P < 0.01). Alanine Ra increased (P < 0.05) during cortisol infusion but remained constant during saline infusion. During cortisol, but not during saline infusion, the rate and percentage of leucine nitrogen going to alanine increased (P < 0.05). Thus, an increase in plasma cortisol within the physiologic range increased proteolysis and the de novo synthesis of alanine, a potential gluconeogenic substrate. Therefore, physiologic changes in plasma cortisol play a role in the regulation of whole body protein and amino acid metabolism in man.
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