title: Physiological hypercortisolemia increases proteolysis, glutamine, and alanine production.
abstract: Physiological elevations of plasma cortisol levels, as are encountered in stress and severe trauma, were produced in six normal subjects by infusing them with 140 micrograms.kg-1.h-1 of hydrocortisone for 64 h. Amino acid kinetics were measured in the postabsorptive state using three 4-h infusions of L-[1-13C]leucine, L-[phenyl-2H5]-phenylalanine, L-[2-15N]glutamine, and L-[1-13C]alanine tracers 1) before, 2) at 12 h, and 3) at 60 h of cortisol infusion. Before and throughout the study, the subjects ate a normal diet of adequate protein (0.8 g.kg-1.day-1) and energy intake. The cortisol infusion raised plasma cortisol levels significantly from 10 +/- 1 to 32 +/- 4 micrograms/dl, leucine flux from 83 +/- 3 to 97 +/- 3 mumol.kg-1.h-1, and phenylalanine flux from 34 +/- 1 to 39 +/- 1 (SE) mumol.kg-1.h-1 after 12 h of cortisol infusion. These increases were maintained until the cortisol infusion was terminated (64 h). These nearly identical 15% increases in two different essential amino acid appearance rates are reflective of increased whole body protein breakdown. Glutamine flux rose from 325 +/- 28 to 453 +/- 28 mumol.kg-1.h-1 by 12 h of cortisol infusion and remained elevated at the same level at 64 h. The increase in flux was primarily due to a 55% increase in glutamine de novo synthesis. Alanine flux increased from 207 +/- 13 to 285 +/- 23 mumol.kg-1.h-1 with acute hypercortisolemia and increased further to 475 +/- 59 mumol.kg-1.h-1 at 60 h of cortisol infusion, a result primarily of increased alanine de novo synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000328:Adult; D000409:Alanine / Q000097:blood*; D005934:Glucagon / Q000097:blood; D005973:Glutamine / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000494:pharmacology; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007930:Leucine / Q000097:blood*; D008297:Male; D010649:Phenylalanine / Q000097:blood*; D011506:Proteins / Q000378:metabolism*; D012016:Reference Values
chemical_list: D007328:Insulin; D011506:Proteins; D005973:Glutamine; D010649:Phenylalanine; D005934:Glucagon; D007930:Leucine; D000409:Alanine; D006854:Hydrocortisone