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

Abstract

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. 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). 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). 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.