Glucocorticoids (GCs) are the most common and effective drugs for treating inflammatory airway
respiratory diseases. Despite their efficacy, some patients respond poorly to GC treatment. Alterations in the expression of the receptor that mediates GC actions, the
glucocorticoid receptor (GR), are one of the potential mechanisms that would explain GC insensitivity. In this review, we present an update on the GR gene and its products, namely GRalphaand
GRbeta, as well as their alterations in disease.
GRalpha has a widespread distribution and is responsible for the induction and repression of target genes, whereas
GRbeta can act as a dominant negative inhibitor of
GRalpha-mediated transactivation and transrepression. Very low
GRbeta mRNA levels have been detected in a number of cells and tissues, which often contradict
GRbeta protein data. Nevertheless, an association between GC insensitivity and increased
GRbeta expression has been reported in
asthma, nasal polyposis, and
ulcerative colitis, and in vitro, certain pro-inflammatory
cytokines upregulate
GRbeta expression. However, the role of
GRbeta in modulating GC sensitivity in vivo has been highly debated and is as yet unclear.