Natural variants of the β isoform of the human glucocorticoid receptor do not alter sensitivity to glucocorticoids

The beta isoform of the human glucocorticoid receptor, hGR beta, is a product of alternative splicing of the hGR gene. The physiological function of this isoform is unknown upto now. Recent data are contradictory in that they either favor or argue against a role of hGR beta as a repressor of the functional hGR alpha isoform. In the present study hGR beta did not inhibit transcriptional activation of the MMTV-driven luciferase reporter gene by dexamethasone-activated hGR alpha in COS-1 cells. In addition, two naturally occurring variants of the hGR beta isoform associated with altered sensitivity to glucocorticoids, termed hGR beta-R23K and hGR beta-N363S, did not repress hGR alpha, even when overexpressed 10-fold. We conclude that the hGR beta isoform, as well as two of its natural variants, do not act as dominant negative inhibitors of hGR alpha function and that the beta isoform does not appear to play a role in the regulation of glucocorticoid sensitivity. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.