Glucocorticoid receptor beta in acute and chronic inflammatory conditions: clinical implications.
Glucocorticoids (GC) are hormones with a wide variety of actions, including profound anti-inflammatory/immunosuppressive effects. Their actions are mediated by an intracellular receptor called the glucocorticoid receptor (GCR). The classical GCR that mediates the hormone response is called GCR alpha. Recently however, many GCR isotypes have been described. A defective GC action has been proposed as an etio-pathogenic mechanism for the development of inflammatory/autoimmune diseases. Inadequate GC actions may have multiple causes such as: defective hypothalamic-pituitary-adrenal axis function, GC export from cells, hormone metabolization into inactive compounds and modifications of the GC receptor, among others. In 1995, a dominant negative effect of a GC receptor isotype termed beta was described; starting a still unsolved controversy about the role of GCR beta as an inducer of GC resistance in certain pathological conditions. The present article will review the data about a possible role for GCR beta in the development of GC resistance in inflammatory diseases. This review will especially focus on the role of the GCR beta in rheumatoid arthritis and in septic shock as examples of a chronic inflammatory disease and an acute systemic inflammatory condition. Original data supporting possible hyperexpression of GCR beta in both conditions will be shown.
Goecke
Annelise
A
Rheumatology Service, Internal Medicine Department, Clinical Hospital, University of Chile, Santiago, Chile. agoecke@med.uchile.cl
Guerrero
Julia
J
D000208:Acute Disease; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D004351:Drug Resistance / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000502:physiology*; D012772:Shock, Septic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D005938:Glucocorticoids; D018836:Inflammation Mediators; D011965:Receptors, Glucocorticoid; C121943:glucocorticoid receptor beta