This Article Full Text Full Text (PDF) All Versions of this Article: 90/5/2994    most recent Author Manuscript (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smit, P. Articles by Koper, J. W. Search for Related Content PubMed PubMed Citation Articles by Smit, P. Articles by Koper, J. W. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB DEXAMETHASONE HYDROCORTISONE Medline Plus Health Information Steroids Related Collections Adrenal and Hypertension

Differential Regulation of Synthetic Glucocorticoids on Gene Expression Levels of Glucocorticoid-Induced Leucine Zipper and Interleukin-2

Departments of Internal Medicine (P.S., H.R., F.H.d.J., S.W.J.L., J.W.K.) and Reproduction and Development (A.O.B.), Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands

Address all correspondence and requests for reprints to: Jan W. Koper, Department of Internal Medicine, Room Ee 585, Erasmus MC, Dr. Molewaterplein 40, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. E-mail: f.koper{at}erasmusmc.nl.

Individual glucocorticoid (GC) sensitivity was determined by measuring the effects of several clinically used GCs on transactivation of the GC-induced leucine zipper (GILZ) gene and on transrepression of the IL-2 gene using quantitative real-time PCR. A clear difference in relative potencies for transactivation and transrepression of the various GCs was observed, suggesting differential effects. To determine whether the in vitro outcomes could predict in vivo effects of GCs, 15 individuals underwent a 0.25-mg dexamethasone (DEX) suppression test (DST) while determining GILZ and IL-2 mRNA levels in their peripheral blood mononuclear cells incubated with hydrocortisone, DEX, budesonide, and prednisolone. No correlations were found between the DST and the two ex-pression assays. However, significant correlations existed between hydrocortisone and DEX (r = 0.52; P = 0.046), hydrocortisone and budesonide (r = 0.48; P = 0.069), and hydrocortisone and prednisolone (r = 0.86; P = 0.007) regarding GILZ mRNA levels, and between hydrocortisone and DEX (r = 0.62; P = 0.014), hydrocortisone and budesonide (r = 0.71; P = 0.003), and hydrocortisone and prednisolone (r = 0.71; P = 0.047) regarding IL-2 mRNA levels. In conclusion, intra- and inter-individual variations in GC sensitivity were observed using two expression assays representing GC-mediated transactivation and transrepression. The two expression assays did not correlate with each other or with the results of the DST. This suggests that regulation of the hypothalamic-pituitary-adrenal axis is more complex. However, within an individual person, these two tests combined might predict what type and dosage of GC will be preferable in individual patients for its inhibitory clinical effects, together with relatively fewer transactivating effects related to adverse effects.

This article has been cited by other articles:

				H. Flaster, J. Bernhagen, T. Calandra, and R. Bucala The Macrophage Migration Inhibitory Factor-Glucocorticoid Dyad: Regulation of Inflammation and Immunity Mol. Endocrinol., June 1, 2007; 21(6): 1267 - 1280. [Abstract] [Full Text] [PDF]

				W. Chen, I. Rogatsky, and M. J. Garabedian MED14 and MED1 Differentially Regulate Target-Specific Gene Activation by the Glucocorticoid Receptor Mol. Endocrinol., March 1, 2006; 20(3): 560 - 572. [Abstract] [Full Text] [PDF]

				H. Russcher, P. Smit, E. F. C. van Rossum, E. L. T. van den Akker, A. O. Brinkmann, L. J. M. de Heide, F. H. de Jong, J. W. Koper, and S. W. J. Lamberts Strategies for the Characterization of Disorders in Cortisol Sensitivity J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 694 - 701. [Abstract] [Full Text] [PDF]

				H. Russcher, P. Smit, E. L. T. van den Akker, E. F. C. van Rossum, A. O. Brinkmann, F. H. de Jong, S. W. J. Lamberts, and J. W. Koper Two Polymorphisms in the Glucocorticoid Receptor Gene Directly Affect Glucocorticoid-Regulated Gene Expression J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5804 - 5810. [Abstract] [Full Text] [PDF]