title: The effect of acute and chronic glucocorticoid excess on leucine kinetics and protein turnover in vivo.
abstract: 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.
mesh_terms: D000308:Adrenocortical Hyperfunction / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D004285:Dogs; D006854:Hydrocortisone / Q000097:blood* / Q000502:physiology; D007700:Kinetics; D007930:Leucine / Q000378:metabolism*; D008954:Models, Biological; D011506:Proteins / Q000378:metabolism*; D013997:Time Factors
chemical_list: D011506:Proteins; D000324:Adrenocorticotropic Hormone; D007930:Leucine; D006854:Hydrocortisone