Glucocorticoid receptor cofactors as therapeutic targets

Numerous transcriptional cofactors (e.g. coactivators, corepressors, and comodulators) are known to alter the maximal transcriptional activity (A(max)) in gene induction and repression by steroid receptors in general and glucocorticoid receptors (GRs) in particular. However, recent data advance the earlier reports that these same factors also modify other parameters of glucocorticoid receptor transcriptional activity: the potency of agonists (or EC₅₀ and the partial agonist activity of antisteroids (or PAA). In several instances, factors modulate the EC₅₀ and/or PAA without changing A(max). Thus, studies of all three parameters reveal new factors acting at various stages of receptor action, thereby increasing the potential therapeutic targets for adjusting GR actions in pathological situations.