The effect of acute and chronic glucocorticoid excess on leucine kinetics and protein turnover in vivo.

The present studies were undertaken to assess the effects of excess cortisol on amino acid exchange in the conscious dog. Three groups of 18-hr fasted dogs with catheters chronically implanted in the femoral artery were studied: Group I (n = 6) received saline; Groups II and III (n = 5, each) received ACTH intravenously (1 U/min) for 7 hr; in addition, Group III received ACTH, 500 U/day intramuscularly for 4 days. Leucine rates of appearance (Ra) and clearance were measured using a constant infusion of L-4,5-[3H]leucine. ACTH treatment resulted in a 9-fold increase in plasma cortisol in Groups II and III (from 2 +/- 1 to 18 +/- 1 and 17 +/- 2 micrograms/dl, in II and III, respectively P less than 0.001), with no effect on either plasma insulin or glucagon. Plasma leucine (mmole/liter) increased from 118 +/- 6 (I) to 153 +/- 6 (II, P less than 0.005) to 275 +/- 35 (III, P less than 0.001). Leucine Ra (micromoles/kilogram/minute) did not change in II, but rose by 39% (P less than 0.005) in III. Clearance (milliliters/kilogram/minute) dropped from 25 +/- 2 (I) to 18 +/- 2 (II, P less than 0.005), to 15 +/- 2 (III, P less than 0.001). It is concluded that acute elevations of cortisol increased plasma leucine only by inhibiting its rate of disposal, whereas chronic elevations had a dual effect; they inhibited leucine disposal and increased its entry into the plasma compartment, suggesting an inhibition of protein synthesis and stimulation of protein breakdown.