Expression of glucocorticoid receptor β in lymphocytes of patients with glucocorticoid-resistant ulcerative colitis

Background & Aims: Recently, the glucocorticoid receptor β (hGRβ) was suggested to play a role as a dominant negative regulator for determining glucocorticoid response. The aim of this study was to clarify whether reverse-transcription polymerase chain reaction (RT-PCR) analysis of hGRβ messenger RNA (mRNA) can predict the response to glucocorticoids in patients with ulcerative colitis. Methods: Total RNA obtained from peripheral blood mononuclear cells (PBMCs) of 23 patients with ulcerative colitis and 20 healthy volunteers was reverse transcribed; the resulting complementary DNA was amplified using specific primers for hGRα and hGRβ. Protein expression of hGR in PBMCs was confirmed by immunoprecipitation–Western blot analysis. Results: The expression of hGRα mRNA (477 base pairs) was detected in all patients and all healthy volunteers. In contrast, a hGRβ mRNA (366 base pairs) was detected in 1 (9.1%) of 11 glucocorticoid-sensitive patients, 10 (83.3%) of 12 glucocorticoid-resistant patients, and 2 (10%) of 20 healthy volunteers. The positive rate of hGRβ mRNA in the resistant group was significantly higher than that in the sensitive group ( P = 0.0019). The hGRβ band could be detected by immunoprecipitation–Western blotting in hGRβ mRNA–positive patients. Conclusions: The results show that the expression of hGRβ mRNA in PBMCs examined by RT-PCR may serve as a novel predictor of glucocorticoid response in ulcerative colitis. GASTROENTEROLOGY 2000;118:859-866