Impact of acute and chronic low-dose glucocorticoids on protein metabolism.
BACKGROUND
High-dose glucocorticoids cause acute protein loss by increasing protein breakdown and oxidation. Whether lower glucocorticoid doses, typical of therapeutic use, induce sustained catabolism has not been studied.


OBJECTIVE
Our objective was to assess the effect of acute and chronic therapeutic glucocorticoid doses on protein metabolism.


METHODS
We conducted an open longitudinal and a cross-sectional study at a clinical research facility.


METHODS
Ten healthy subjects were studied before and after a short course of prednisolone (5 and 10 mg/d sequentially for 7 d each). Twelve subjects with inactive polymyalgia rheumatica receiving chronic (>12 months) prednisone (mean = 5.0 +/- 0.8 mg/d) were compared with 12 age- and gender-matched normal subjects.


METHODS
Whole-body protein metabolism was assessed using a 3-h primed constant infusion of 1-[(13)C]leucine, from which rates of leucine appearance (leucine Ra, an index of protein breakdown), leucine oxidation (Lox, index of protein oxidation) and leucine incorporation into protein (LIP, index of protein synthesis) were estimated.


RESULTS
Prednisolone induced an acute significant increase in Lox (P = 0.008) and a fall in LIP (P = 0.08) but did not affect leucine Ra. There was no significant difference between the effects of the 5- and 10-mg prednisolone doses on leucine metabolism. In subjects receiving chronic prednisone therapy, leucine Ra, Lox, and LIP were not significantly different from normal subjects.


CONCLUSIONS
Glucocorticoids stimulate protein oxidation after acute but not chronic administration. This time-related change suggests that glucocorticoid-induced stimulation of protein oxidation does not persist but that a metabolic adaptation occurs to limit protein loss.
Burt
Morton G
MG
Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.
Johannsson
Gudmundur
G
Umpleby
A Margot
AM
Chisholm
Donald J
DJ
Ho
Ken K Y
KK
D000368:Aged; D002247:Carbon Isotopes; D003430:Cross-Sectional Studies; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007930:Leucine / Q000493:pharmacokinetics; D008137:Longitudinal Studies; D008297:Male; D008660:Metabolism / Q000187:drug effects; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D011239:Prednisolone / Q000008:administration & dosage*; D011506:Proteins / Q000378:metabolism*; D012044:Regression Analysis
D002247:Carbon Isotopes; D005938:Glucocorticoids; D011506:Proteins; D011239:Prednisolone; D007930:Leucine