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

Additional Metadata
Keywords Dominant negative inhibitor, hGRβ, Point mutations, Splice variant, Transcriptional activation
Persistent URL dx.doi.org/10.1016/S0303-7207(99)00072-6, hdl.handle.net/1765/61530
Journal Molecular and Cellular Endocrinology
Citation
de Lange, P, Koper, J.W, Brinkmann, A.O, de Jong, F.H, & Lamberts, S.W.J. (1999). Natural variants of the β isoform of the human glucocorticoid receptor do not alter sensitivity to glucocorticoids. Molecular and Cellular Endocrinology, 153(1-2), 163–168. doi:10.1016/S0303-7207(99)00072-6