ZINC REVERSIBLY INHIBITS STEROID-BINDING TO MURINE GLUCOCORTICOID RECEPTOR

Previous work, has demonstrated that several transition metals and the ir anions, including cadmium, arsenite, and selenite, can inhibit gluc ocorticoid binding to glucocorticoid receptors in vitro, In this study , we demonstrated that in vitro zinc can also inhibit the binding of g lucocorticoids to their receptor at relatively modest concentrations ( 10 to 100 mu M), This inhibition was demonstrated in both crude and im munopurified receptor preparations and was reversible following remova l of zinc. Inhibition could also be reversed by-addition of the reduci ng agent dithiothreitol (DTT), This suggested that zinc might be actin g by interacting with the vicinal dithiols in the steroid binding regi on of the receptor as previously described for other transition metals and anions, The ability of a biologically important trace metal to bl och steroid binding suggests a role for zinc in the regulation of gluc ocorticoid receptor-ligand interactions and may explain the ability of zinc to block glucocorticoid-induced apoptosis, (C) 1997 Academic Pre ss.