The kinetics of binding to the molybdate-stabilized glucocorticoid receptor of rat thymus cytosol were determined at 0 degrees C for a number of glucocorticoid agonists and antagonists. Equilibrium constants derived from the rate constants for association and dissociation were in good agreement with those determined directly or by competition under equilibrium conditions. Kinetics parameters for the slowly dissociating form of binding detected by a non-equilibrium dextran/charcoal competitive binding assay reflected the nature and extent of functional-group substitution on the steroid nucleus, but bore no relation to the classification of steroids as glucocorticoid agonists or antagonists. It is concluded that the binding of antagonists that is detected by such methods is agonist-like binding, which is not relevant to their antiglucocorticoid actions. Both agonists and antagonists displayed Michaelis-Menten association kinetics, but this behaviour was much more pronounced for antagonists. This is attributed to the existence of a second form of steroid-receptor complex, which escapes detection by the usual assay methods as a result of a high rate of dissociation and which is quantitatively antagonist-specific under equilibrium conditions. Direct evidence for the existence of two forms of antagonist-receptor complex was provided by results showing that the dissociation of the glucocorticoid antagonist progesterone from the receptor was biphasic.

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