Relationship between glucocorticoid receptor and response to glucocorticoid therapy in ulcerative colitis

被引:24
作者
Shimada, T [1 ]
Hiwatashi, N [1 ]
Yamazaki, H [1 ]
Kinouchi, Y [1 ]
Toyota, T [1 ]
机构
[1] TOHOKU UNIV,SCH MED,DEPT INTERNAL MED 3,AOBA KU,SENDAI,MIYAGI 98077,JAPAN
关键词
ulcerative colitis; glucocorticoid receptor; glucocorticoid resistance; whole-cell binding assay;
D O I
10.1007/BF02062021
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
PURPOSE: To clarify the relationship between the glucocorticoid receptor and the effectiveness of glucocorticoid therapy in patients with ulcerative colitis, we investigated the number and apparent dissociation constant of glucocorticoid receptor in peripheral blood mononuclear leukocytes of patients with ulcerative colitis. MATERIALS AND METHODS: Eleven patients with ulcerative colitis (5 who responded to intravenous glucocorticoids and 6 who did not) and ten control subjects were studied. The number and apparent dissociation constant of glucocorticoid receptor were measured using a whole-cell binding assay. Results were expressed as a median (interquartile range). RESULTS: The number of glucocorticoid receptors from the six nonresponders, five responders, and ten healthy controls were 4922 (range, 4484-5643), 3413 (range, 3183-4450), and 3610 (range, 2594-3979) binding sites/cell, respectively. The apparent dissociation constant of the glucocorticoid receptors from the nonresponders, responders, and healthy controls were 7.03 (range, 5.66-10), 4.27 (range, 4-5.13), and 6.18 (range, 5.86-6.74) nM, respectively. Nonresponders had a significant increase both in the number of binding sites and in the apparent dissociation constant compared with responders (P = 0.045; P = 0.029). CONCLUSIONS: The increased number and apparent dissociation constant of glucocorticoid receptor are closely associated with the effectiveness of glucocorticoid therapy. The measurement of the number and apparent dissociation constant of glucocorticoid receptor may be useful in predicting response to glucocorticoids.
引用
收藏
页码:S54 / S58
页数:5
相关论文
共 24 条
[21]   STEROID-RESISTANT ASTHMA - CELLULAR MECHANISMS CONTRIBUTING TO INADEQUATE RESPONSE TO GLUCOCORTICOID THERAPY [J].
SHER, ER ;
LEUNG, DYM ;
SURS, W ;
KAM, JC ;
ZIEG, G ;
KAMADA, AK ;
SZEFLER, SJ .
JOURNAL OF CLINICAL INVESTIGATION, 1994, 93 (01) :33-39
[22]  
TRUELOVE SC, 1974, LANCET, V1, P1067
[23]   CORTISONE IN ULCERATIVE COLITIS - FINAL REPORT ON A THERAPEUTIC TRIAL [J].
TRUELOVE, SC ;
WITTS, LJ .
BRITISH MEDICAL JOURNAL, 1955, 2 (OCT29) :1041-1048
[24]   TRANSCRIPTIONAL INTERFERENCE BETWEEN C-JUN AND THE GLUCOCORTICOID RECEPTOR - MUTUAL INHIBITION OF DNA-BINDING DUE TO DIRECT PROTEIN PROTEIN-INTERACTION [J].
YANGYEN, HF ;
CHAMBARD, JC ;
SUN, YL ;
SMEAL, T ;
SCHMIDT, TJ ;
DROUIN, J ;
KARIN, M .
CELL, 1990, 62 (06) :1205-1215