Glucocorticoid receptors in human synovial tissue and relative receptor affinities of glucocorticoid-21-esters.

A dexamethasone binding protein was detected in cytosol of 11 human synovial tissues from patients with chronic polyarthritis. The apparent dissociation constant (KD) ranged from 3.3 to 17.1 (mean, 7.0 +/- 4.3) nmol/liter, and the receptor concentration (Ro) from 17 to 65 (mean, 42 + 15) fmol/mg protein. Results of competition assays with an excess of unlabeled aldosterone, estradiol, pregnenolone, and testosterone confirmed that the binding protein had characteristics of a glucocorticoid receptor. With the use of diisopropylfluorophosphate (DFP) for esterase inhibition, and considering the purity of the starting material and the hydrolysis products, we could determine the relative receptor affinities of glucocorticoid-21-esters. In contrast to the high affinity of the glucocorticoid-17-ester examined, esterification in position 21 abolishes binding affinities. Glucocorticoid-21-esters are true prodrugs for which the glucocorticoid action is caused only by the corresponding glucocorticoid alcohol.