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.
Simons
S Stoney
SS
Steroid Hormones Section, Bldg. 10, Room 8N-307B, NIDDK/CEB, National Institutes of Health (NIH), Bethesda, MD 20892-1772, USA. steroids@helix.nih.gov
D000818:Animals; D002460:Cell Line; D056970:Co-Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D054333:Drug Partial Agonism; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D056918:Nuclear Receptor Coactivators / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011965:Receptors, Glucocorticoid / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D056970:Co-Repressor Proteins; D005938:Glucocorticoids; D056918:Nuclear Receptor Coactivators; D011965:Receptors, Glucocorticoid; D012097:Repressor Proteins; D014157:Transcription Factors
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