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

Gastroenterology. 2000 May;118(5):859-66. doi: 10.1016/s0016-5085(00)70172-7.

Abstract

Background & aims: Recently, the glucocorticoid receptor beta (hGRbeta) 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 hGRbeta 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 hGRalpha and hGRbeta. Protein expression of hGR in PBMCs was confirmed by immunoprecipitation-Western blot analysis.

Results: The expression of hGRalpha mRNA (477 base pairs) was detected in all patients and all healthy volunteers. In contrast, a hGRbeta 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 hGRbeta mRNA in the resistant group was significantly higher than that in the sensitive group (P = 0.0019). The hGRbeta band could be detected by immunoprecipitation-Western blotting in hGRbeta mRNA-positive patients.

Conclusions: The results show that the expression of hGRbeta mRNA in PBMCs examined by RT-PCR may serve as a novel predictor of glucocorticoid response in ulcerative colitis.

MeSH terms

  • Adolescent
  • Adult
  • Colitis, Ulcerative / blood
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / metabolism*
  • Drug Resistance
  • Female
  • Glucocorticoids / therapeutic use*
  • Humans
  • Lymphocytes / metabolism*
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Glucocorticoids
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • glucocorticoid receptor beta