Homologous Down-Regulation of the Glucocorticoid Receptor Down-Modulates Cellular Hormone Responsiveness in HumanHistiocytic Lymphoma U937 Cells

Abstract

One of the determinants of cellular responsiveness to glucocorticoid hormone is the concentration of the receptorprotein. It is well-known that cellular receptor levels are down-regulated by the cognate ligands, butthe 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 glucocorticoid receptor was homologously down-regulated by means of both ligand binding and Western immunoblot experiments. Reduction of the receptor was saturable, and the receptor levels tended to return to the levels before treatment after 3-day culture in the presence of the hormone. Next, using the cells which were pretreated with the hormone for 0 to 3 days, hormonal inducibility of the transiently-transfected reporter gene and the inhibitory effect of the hormone on cellular 3-O-methyl glucose uptake were determined. Hormonal inducibility of the reporter gene was progressively reduced, and thereafter tended to be restored, apparently in accordance with the cyclic change in amount of the receptor. The glucose uptake inhibiting effect of the hormone also revealed this cyclic pattern. In summary, in U937 cells glucocorticoid receptor was homologously down-regulated and may play a pivotal role in attenuating hormone responsiveness. © 1994, The Japan Endocrine Society. All rights reserved.