Fukawa E, Tanaka H, Makino Y, Hirano F, Akama H, Kawai S, Makino I
Second Department of Internal Medicine, Asahikawa Medical College, Japan.
Endocr J. 1994 Dec;41(6):623-30. doi: 10.1507/endocrj.41.623.
One of the determinants of cellular responsiveness to glucocorticoid hormone is the concentration of the receptor protein. It is well-known that cellular receptor levels are down-regulated by the cognate ligands, 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 glucorticoid 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.
细胞对糖皮质激素的反应性的决定因素之一是受体蛋白的浓度。众所周知，细胞受体水平会被同源配体下调，但这种受体同源下调的生物学意义尚未完全明了。我们通过配体结合实验和蛋白质免疫印迹实验表明，在人组织细胞淋巴瘤细胞系U937中，细胞糖皮质激素受体发生了同源下调。受体的减少具有饱和性，并且在激素存在的情况下培养3天后，受体水平倾向于恢复到处理前的水平。接下来，使用经激素预处理0至3天的细胞，测定瞬时转染报告基因的激素诱导性以及激素对细胞3 - O - 甲基葡萄糖摄取的抑制作用。报告基因的激素诱导性逐渐降低，随后明显根据受体数量的周期性变化趋于恢复。激素对葡萄糖摄取的抑制作用也呈现出这种周期性模式。总之，在U937细胞中，糖皮质激素受体发生同源下调，可能在减弱激素反应性方面起关键作用。
