Deuterium isotope effects on the rates of steroid--glucocorticoid receptor interactions.

Rate constants of association and dissociation of several steroids to and from glucocorticoid receptor protein of chick thymus cytosol were determined in water and deuterium oxide. Substitution of deuterium for hydrogen did not influence association rate constants. Dissociation rate constants decreased about twofold in deuterium oxide in case of steroids containing an 11-beta-hydroxyl group but remained unchanged if the steroid had no hydroxyl or had an alpha-hydroxyl group at position 11. Presence of molybdate ions decreased but did not abolish the deuterium isotope effect. These findings suggest that the 11-beta-hydroxyl group, known to be present in every optimal glucocorticoid agonist molecule, participates in a kinetically relevant hydrogen bond, and that this hydrogen bond may have a role in glucocorticoid action.