HOMOLOGOUS DOWN-REGULATION OF THE GLUCOCORTICOID RECEPTOR DOWN-MODULATES CELLULAR HORMONE RESPONSIVENESS IN HUMAN HISTIOCYTIC LYMPHOMA U937CELLS

One of the determinants of cellular responsiveness to glucocorticoid h ormone is the concentration of the receptor protein. It is well-known that cellular receptor levels are down-regulated by the cognate ligand s, but the biological significance of this homologous down-regulation of the receptor has not yet been completely understood. We showed that in human histiocytic lymphoma cell line U937 the cellular glucocortic oid receptor was homologously down-regulated by means of both ligand b inding and Western immunoblot experiments. Reduction of the receptor w as saturable, and the receptor levels tended to return to the levels b efore treatment after 3-day culture in the presence of the hormone. Ne xt, using the cells which were pretreated with the hormone for 0 to 3 days, hormonal inducibility of the transiently-transfected reporter ge ne and the inhibitory effect of the hormone on cellular 3-O-methyl glu cose uptake were determined. Hormonal inducibility of the reporter gen e was progressively reduced, and thereafter tended to be restored, app arently in accordance with the cyclic change in amount of the receptor . The glucose uptake inhibiting effect of the hormone also revealed th is cyclic pattern. In summary, in U937 cells glucocorticoid