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
[1]   STEROID-RESISTANT ASTHMA - IMMUNOLOGICAL AND PHARMACOLOGICAL FEATURES [J].
ALVAREZ, J ;
SURS, W ;
LEUNG, DYM ;
IKLE, D ;
GELFAND, EW ;
SZEFLER, SJ .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 1992, 89 (03) :714-721
[2]  
BRANDON DD, 1989, CANCER RES, V49, pS2203
[3]   PRIMARY CORTISOL RESISTANCE ASSOCIATED WITH A THERMOLABILE GLUCOCORTICOID RECEPTOR IN A PATIENT WITH FATIGUE AS THE ONLY SYMPTOM [J].
BRONNEGARD, M ;
WERNER, S ;
GUSTAFSSON, JA .
JOURNAL OF CLINICAL INVESTIGATION, 1986, 78 (05) :1270-1278
[4]   THE COMMON 90-KD PROTEIN-COMPONENT OF NON-TRANSFORMED 8S STEROID-RECEPTORS IS A HEAT-SHOCK PROTEIN [J].
CATELLI, MG ;
BINART, N ;
JUNGTESTAS, I ;
RENOIR, JM ;
BAULIEU, EE ;
FERAMISCO, JR ;
WELCH, WJ .
EMBO JOURNAL, 1985, 4 (12) :3131-3135
[5]   GLUCOCORTICOID EFFECTS ON THE PRODUCTION AND ACTIONS OF IMMUNE CYTOKINES [J].
GUYRE, PM ;
GIRARD, MT ;
MORGANELLI, PM ;
MANGANIELLO, PD .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1988, 30 (1-6) :89-93
[6]   POINT MUTATION CAUSING A SINGLE AMINO-ACID SUBSTITUTION IN THE HORMONE BINDING DOMAIN OF THE GLUCOCORTICOID RECEPTOR IN FAMILIAL GLUCOCORTICOID RESISTANCE [J].
HURLEY, DM ;
ACCILI, D ;
STRATAKIS, CA ;
KARL, M ;
VAMVAKOPOULOS, N ;
RORER, E ;
CONSTANTINE, K ;
TAYLOR, SI ;
CHROUSOS, GP .
JOURNAL OF CLINICAL INVESTIGATION, 1991, 87 (02) :680-686
[7]   PRIMARY CORTISOL RESISTANCE ACCOMPANIED BY A REDUCTION IN GLUCOCORTICOID RECEPTORS IN 2 MEMBERS OF THE SAME FAMILY [J].
IIDA, S ;
GOMI, M ;
MORIWAKI, K ;
ITOH, Y ;
HIROBE, K ;
MATSUZAWA, Y ;
KATAGIRI, S ;
YONEZAWA, T ;
TARUI, S .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1985, 60 (05) :967-971
[8]   ANTITUMOR PROMOTION AND ANTIINFLAMMATION - DOWN-MODULATION OF AP-1 (FOS JUN) ACTIVITY BY GLUCOCORTICOID HORMONE [J].
JONAT, C ;
RAHMSDORF, HJ ;
PARK, KK ;
CATO, ACB ;
GEBEL, S ;
PONTA, H ;
HERRLICH, P .
CELL, 1990, 62 (06) :1189-1204
[9]   DEXAMETHASONE INHIBITION OF INTERLEUKIN-1 BETA-PRODUCTION BY HUMAN-MONOCYTES - POSTTRANSCRIPTIONAL MECHANISMS [J].
KERN, JA ;
LAMB, RJ ;
REED, JC ;
DANIELE, RP ;
NOWELL, PC .
JOURNAL OF CLINICAL INVESTIGATION, 1988, 81 (01) :237-244
[10]  
KRISTENSEN M, 1974, SCAND J GASTROENTERO, V9, P177