Mechanism of dexamethasone inhibition of plasminogen activator in rat hepatoma cells.

Glucocorticoids rapidly and completely inhibit intracellular plasminogen activator activity in rat hepatoma cells, as assayed by the solubilization of 125I-labeled fibrin. Experiments in which extracts of dexamethasone-treated cells are mixed with extracts of control cells demonstrate an inhibitor of protease activity. Plasminogen activator is found primarily in the particulate fraction of cell lysates, whereas the inhibitor is localized in the soluble fraction. Variant cells have been isolated previously that are fully resistant to the dexamethoasone inhibition of plasminogen activator activity. These variants have no demonstrable inhibitor activity, whereas plasminogen activator in these cells is fully sensitive to inhibitor from wild-type cells. Thus, the basis for hormone resistance appears to be the failure of dexamethasone to induce an inhibitor.