Regulation of glucocorticoid receptor gamma (GRgamma) by glucocorticoid receptor haplotype and glucocorticoid

Clinical Endocrinology
Adam StevensDavid Ray

Abstract

To measure glucocorticoid receptor gamma (GRgamma) expression in transformed lymphocytes from individuals of known GR gene haplotype. Recently, a glucocorticoid receptor haplotype (GAT) has been described that associates with increased sensitivity to dexamethasone. As there is strong linkage disequilibrium across the gene, this haplotype is likely to extend through exon 3, altered splicing of which generates the GRgamma isoform, a splice variant with impaired transactivation activity. Therefore we proposed that the GR haplotype affects glucocorticoid sensitivity either by influencing GRgamma expression basally, or in response to Gc exposure. We have measured expression of GRgamma, using a validated RT-PCR assay in human B lymphoblast cells of known haplotype under basal conditions, and after dexamethasone treatment. The A549 human lung cell line and normal volunteers, five with the GAT GR haplotype and three with the CGA haplotype. Relative expression of GRgamma compared to total GR mRNA. GRgamma made up 5-6% of all the GR transcripts. There was no effect of carriage of the GR gene GAT haplotype on this expression. There was no effect of dexamethasone on relative expression of GRgamma. We propose that the GRgamma isoform is a p...Continue Reading

References

Apr 23, 2002·Nature Reviews. Genetics·Luca CartegniAdrian R Krainer
Jul 12, 2002·Nature·Tom Maniatis, Bosiljka Tasic
Jul 26, 2002·The Journal of Steroid Biochemistry and Molecular Biology·R H DeRijkE R de Kloet
Feb 7, 2004·The Journal of Clinical Endocrinology and Metabolism·Adam StevensRachelle Donn

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Citations

Dec 20, 2011·Blood Reviews·Anna Rita MigliaccioCarolyn Whitsett
Jan 13, 2006·British Journal of Pharmacology·Julia C Buckingham
Dec 23, 2006·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Rachelle DonnDavid Ray
May 1, 2006·Expert Review of Endocrinology & Metabolism·David W RayAndrew Berry

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