Loss of glucocorticoid regulation of plasminogen activator activity in anucleate rat hepatoma cells . Biochem

Summary: Glucocorticoids decrease the plasminogen activator activity of rat hepatoma cells through production of an inhibitor. We have examined the dexamethasone regulation of plasminogen activator in anucleate rat hepatoma cells to investigate the role of the nucleus in the steroid regulation of this membrane-associated phenomenon. Dexamethasone did not affect either the intra- or extra-cellular plasminogen activator activity of the anucleate cells, and did not induce production of an inhibitor of plasminogen acti-vator. Therefore, glucocorticoid regulation of plasminogen activator activ-ity requires the presence of an intact nucleus. Glucocorticoids alter several membrane-associated properties in hepatoma tissue culture (HTC) 1 cells, an established line of rat hepatoma cells (1). Dexamethasone, a synthetic glucocorticoid, decreases both the intra- and extra-cellular activity of plasminogen activator (2,3), a serine protease which catalyzes the conversion of the serum protein, plasminogen, to the active fibrinolysin, plasmin. Seifert and Gelehrter (4) have previously reported that the mechanism of dexamethasone-induced inhibition of plasmin-ogen activator (PA) activity appears to be the production of an inhibitor of PA. Steroid hormones are thought to induce cellular changes through tran-scriptional activation of specific genes after translocation of cytosol hormone-receptor complexes into the nucleus and site-specific binding of the complexes to the chromatin (5). However, steroid hormones or hormone-receptor complexes might also mediate cellular changes by directly affect-ing cytoplasmic or membrane functions. To investigate these alternative mechanisms for steroid hormone action, we examined the glucocorticoi