Relationship between expression of glucocorticoid receptor isoforms and glucocorticoid resistance in immune thrombocytopenia.

Background: Glucocorticoids (GCs) play an important role in the treatment of several hematological malignancies, such as immune thrombocytopenia (ITP). The glucocorticoid receptor (GR) mediates the effects of GCs. Five isoforms of GR mRNA were described: GR alpha, GR beta, GR gamma, GRP, and GRA. GR levels are regulated by alternative splicing of GR mRNA. Several studies demonstrated that a lower GR expression was associated with poor GC response. Purpose: This study investigated the expression of GR isoforms and the relationship between GC resistance in ITP. Methods: This study determined GR alpha/beta/gamma/P mRNA and GR alpha/beta protein expression levels using SYBR Green Real-time PCR and Western blot, respectively, in 49 newly diagnosed ITP patients and 31 controls. Results: The expression of GR isoform mRNA in ITP and controls showed the following trend: GR alpha > GRP > GR gamma > GR beta. The expression of GR alpha, beta mRNA and the total frequency of the four GR isoforms in ITP was significantly higher than in controls (P < 0.05). The expression of GR alpha mRNA and protein in the GC-resistant group was significantly lower than that in the GC-sensitive group and controls (P < 0.05). GR beta could not be detected at the protein level in our experimental conditions. Conclusion: GR alpha and GRP were the main GR isoforms responsible for the effects of GC, and GR alpha and GRP exhibited synergistic effects. The down-regulation of GR alpha levels may play an important role in GC resistance in ITP. The effects of GCs in ITP were not associated with changes in GR beta and GR gamma.