Correlation between different gene expression assays designed to measure trans-activation potencies of systemic glucocorticoids.
The glucocorticoids (GC) betamethasone, dexamethasone, hydrocortisone, methylprednisolone, prednisolone and triamcinolone acetonide are currently used in the treatment of inflammatory diseases. Through a process called trans-activation, GC activate gene expression and produce various physiological and pharmacological effects. In particular, by inducing gluconeogenic enzymes, long-term GC treatment may cause diabetes. Using three different assays, we have extensively compared the capacity of the above GC to activate gene expression. trans-Activation of a GC inducible luciferase gene was assessed in HeLa and A549 cells after stable and transient transfection, respectively. In hepatoma tissue culture cells, we measured trans-activation of the endogenous gene encoding tyrosine aminotransferase, a gluconeogenic enzyme. Half-maximal effective concentrations of GC were determined by dose-response analyses. Results obtained with these assays were highly correlated and GC were ranked in three groups according to their trans-activation potency: betamethasone, dexamethasone, and triamcinolone acetonide > methylprednisolone and prednisolone > hydrocortisone. Potencies were not strictly related to receptor binding affinities and not significantly affected by the amount of endogenous GC receptor.
Jaffuel
D
D
Institut National de la Santé et de la Recherche Médicale U454-IFR3 and Service des Maladies Respiratoires, CHU de Montpellier, 34295 5, Montpellier Cedex, France.
Roumestan
C
C
Balaguer
P
P
Henriquet
C
C
Gougat
C
C
Bousquet
J
J
Demoly
P
P
Mathieu
M
M
D004305:Dose-Response Relationship, Drug; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008156:Luciferases / Q000235:genetics; D015203:Reproducibility of Results; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D014444:Tyrosine Transaminase / Q000235:genetics
D005938:Glucocorticoids; D008156:Luciferases; D014444:Tyrosine Transaminase