Correlation between different gene expression assays designed to measure trans-activation potencies of systemic glucocorticoids

The glucocorticoids (GC) betamethasone, dexamethasone, hydrocortisone, meth ylprednisolone, 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 a nd pharmacological effects. In particular, by inducing gluconeogenic enzyme s, 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 assesse d in HeLa and A549 cells after stable and transient transfection, respectiv ely. 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-respon se 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 > methylpredniso lone and prednisolone > hydrocortisone. Potencies were not strictly related to receptor binding affinities and not significantly affected by the amoun t of endogenous GC receptor. (C) 2001 Elsevier Science Inc. Ah rights reser ved.