Glucocorticoid receptor (GR) β has intrinsic, GRα-independent transcriptional activity

The human glucocorticoid receptor (GR) gene produces C-terminal GR beta and GR alpha isoforms through alternative use of specific exons 9 beta and alpha, respectively. We explored the transcriptional activity of GR beta on endogenous genes by developing HeLa cells stably expressing EGFP-GR beta or EGFP. Microarray analyses revealed that GR beta had intrinsic gene-specific transcriptional activity, regulating mRNA expression of a large number of genes negatively or positively. Majority of GR beta-responsive genes was distinct from those modulated by GR alpha, while GR beta and GR alpha mutually modulated each other's transcriptional activity in a subpopulation of genes. We did not observe in HCT116 cells nuclear translocation of GR beta and activation of this receptor by RU 486, a synthetic steroid previously reported to bind GR beta and to induce nuclear translocation. Our results indicate that GR beta has intrinsic, GR alpha-independent, gene-specific transcriptional activity, in addition to its previously reported dominant negative effect on GR alpha-induced transactivation of GRE-driven promoters. Published by Elsevier Inc.