Expression Of Glucocorticoid Receptor Isoforms And The Relationship Between Glucocorticoid Receptor Isoforms And Glucocorticoid Resistance In Idiopathic Thrombocytopenic Purpura

Objective: To investigate the expression of glucocorticoid receptor (GR) α, β, γand P in idiopathic thrombocytopenic purpura(ITP) and in controls, as well as todetermine the relationship between GR isoforms and glucocorticoid (GC) resistance inITP.Methods: We collected49newly diagnosed patients with ITP (16male;33female; median age34) from the Hematology department of First Affiliated hospital ofDalian Medical University from July2009to March2011. Among the49newlydiagnosed patients with ITP,32of them were treated by GC. The32patients werefurther divided into two groups according to GC efficacy: the GC-sensitive group (5male;17female; median age30.5) and the GC-resistance group (5male;5female;median age47.5).31volunteers with normal parameters from blood donors wereselected as controls (11male;20female; median age34). The mRNA expression ofGRα, β, γ and P in all subjects was detected by Real-time RT PCR (SYBR Green I).The protein expression of GRα and β was detected by Western blot.Results: The mRNA expression of GRα, β and the total frequency of the fourisoforms (GRα, β, γ and P) in ITP was significantly higher than controls(P<0.05). GRαand GRP showed a positive correlation in ITP and controls, the correlation coefficientwas0.48，0.69respectively (P<0.05). The mRNA expression of the four isoforms inITP and controls showed following trend: GRα﹥GRP﹥GRγ﹥GRβ. The frequency ofα, P, γ and β expression in ITP was58.91%,23.76%,13.37%,3.96%respectively,while in the control group, it was47.32%,33.04%,18.69%,1.79%respectively.Compared to GC-sensitive group, in GC-resistant group, there was increased expressionof GRγ mRNA, whereas GRα, GRP and GRβ mRNA expression was decreased，but no significant difference was observed between the two groups. The protein expression ofGRα was significantly lower in GC-resistance group than the GC-sensitive group andcontrols (P<0.05). GRα/GRγ ratio was lower in the GC-resistance group (2.02) than theGC-sensitive group(5.55) and controls(2.65). GRβ could not be detected at the proteinlevel. The difference of GR isoforms mRNA expression in ITP was significantly largerthan that in controls (ITP:GRα:0.05-12.47, GRβ:0-25.81, GRγ:0-380.04, GRP:0-359.54;Contros:GRα:0.09-2.04, GRβ:0-3.16, GRγ:0-2.28, GRP:0-15.14).Conclusion: The mRNA expression of GRα, GRβ and the total frequency of thefour isoforms (α, β, γ and P) in ITP was significantly higher than that in controls. GRαand GRP accounted for higher occurrence of the four isoforms. In addition, GRαshowed a positive correlation with GRP. The changes in expression of α and P may playan imporptant role in GC efficacy and GC resistance.The protein expression of GRαwas decreased significantly in GC-resistance group. The increased expression of GRγand decreased expression of GRα and GRP may contribute to GC resistance in ITP.There was significantly larger difference of GR isoforms mRNA expression in ITP thanin controls, this phenomenon prompts that the treatment of ITP shoud be individualizedto overcome GC resistance.