title: Impact of acute and chronic low-dose glucocorticoids on protein metabolism.
abstract: 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.
authors.affiliation: Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Morton G
authors.initials: MG
authors.lastname: Burt
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
authors.forename: A Margot
authors.initials: AM
authors.lastname: Umpleby
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Chisholm
authors.forename: Ken K Y
authors.initials: KK
authors.lastname: Ho
mesh_terms: 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
chemical_list: D002247:Carbon Isotopes; D005938:Glucocorticoids; D011506:Proteins; D011239:Prednisolone; D007930:Leucine