Endocrinology, Vol 133, 248-256, Copyright © 1993 by Endocrine Society

ARTICLES

Differential autoregulation of glucocorticoid receptor expression in human T- and B-cell lines

RR Denton, LP Eisen, MS Elsasser and JM Harmon
Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.

Regulation of glucocorticoid receptor (GR) expression by its cognate ligand was examined in the glucocorticoid-sensitive human leukemic T- cell line 6TG1.1 and in the human B-cell line IM-9. In contrast to the decrease in GR mRNA seen in IM-9 cells after treatment with 1 microM dexamethasone for 16-18 h, treatment of 6TG1.1 cells resulted in an 8- fold increase in GR mRNA, as determined by Northern blot and RNase protection analysis, with a corresponding 3- to 4-fold increase in GR protein. Half-maximal induction of GR mRNA and protein in 6TG1.1 cells was observed between 10-100 nM dexamethasone, and inclusion of 1 microM RU 38486 completely blocked the effects of 100 nM dexamethasone, demonstrating that positive autoregulation of GR expression in 6TG1.1 cells is a receptor-mediated response. Positive autoregulation of GR expression was also observed in glucocorticoid-resistant CEM-C1 cells, which contain functional GR, but whose growth is unaffected by glucocorticoids. Thus, positive autoregulation is neither a consequence nor the sole cause of growth arrest. The degree of negative autoregulation in IM-9 cells and positive autoregulation in 6TG1.1 cells was unaffected by inhibition of protein synthesis with cycloheximide. Measurement of GR mRNA turnover in 6TG1.1 cells treated with actinomycin-D revealed a half-life of 2.5 h, which was unaffected by dexamethasone treatment. A similar half-life was determined in IM-9 cells and was also unaffected by steroid treatment. These results are consistent with the interpretation that glucocorticoid-mediated autoregulation of GR expression is a tissue-specific primary transcriptional response.

This article has been cited by other articles:

				W. L. Whittle, A. C. Holloway, S. Lye, J. R. G. Challis, and W. Gibb The Pattern of Glucocorticoid and Estrogen Receptors May Explain Differences in Steroid Dependency of Intrauterine Prostaglandin Production at Parturition in Sheep Reproductive Sciences, October 1, 2006; 13(7): 506 - 511. [Abstract] [PDF]

				W. J. E. Tissing, J. P. P. Meijerink, B. Brinkhof, M. J. C. Broekhuis, R. X. Menezes, M. L. den Boer, and R. Pieters Glucocorticoid-induced glucocorticoid-receptor expression and promoter usage is not linked to glucocorticoid resistance in childhood ALL Blood, August 1, 2006; 108(3): 1045 - 1049. [Abstract] [Full Text] [PDF]

				P. S. Bachmann, R. Gorman, K. L. MacKenzie, L. Lutze-Mann, and R. B. Lock Dexamethasone resistance in B-cell precursor childhood acute lymphoblastic leukemia occurs downstream of ligand-induced nuclear translocation of the glucocorticoid receptor Blood, March 15, 2005; 105(6): 2519 - 2526. [Abstract] [Full Text] [PDF]

				B. M. Necela and J. A. Cidlowski Mechanisms of Glucocorticoid Receptor Action in Noninflammatory and Inflammatory Cells Proceedings of the ATS, November 1, 2004; 1(3): 239 - 246. [Full Text] [PDF]

				J. F. Purton, J. A. Monk, D. R. Liddicoat, K. Kyparissoudis, S. Sakkal, S. J. Richardson, D. I. Godfrey, and T. J. Cole Expression of the Glucocorticoid Receptor from the 1A Promoter Correlates with T Lymphocyte Sensitivity to Glucocorticoid-Induced Cell Death J. Immunol., September 15, 2004; 173(6): 3816 - 3824. [Abstract] [Full Text] [PDF]

				M. B. Breslin, C.-D. Geng, and W. V. Vedeckis Multiple Promoters Exist in the Human GR Gene, One of Which Is Activated by Glucocorticoids Mol. Endocrinol., August 1, 2001; 15(8): 1381 - 1395. [Abstract] [Full Text] [PDF]

				L. Pujols, J. Mullol, M. Pérez, J. Roca-Ferrer, M. Juan, A. Xaubet, J. A. Cidlowski, and C. Picado Expression of the Human Glucocorticoid Receptor {alpha} and {beta} Isoforms in Human Respiratory Epithelial Cells and Their Regulation by Dexamethasone Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 49 - 57. [Abstract] [Full Text]

				R. Dimri, Y. Sharabi, and J. Shoham Specific Inhibition of Glucocorticoid-Induced Thymocyte Apoptosis by Substance P J. Immunol., March 1, 2000; 164(5): 2479 - 2486. [Abstract] [Full Text] [PDF]

				R. M. ASAINZ, J. C. MAYO, R. J. REITER, I. ANTOLÍN, M. M. ESTEBAN, and C. RODRÍGUEZ Melatonin regulates glucocorticoid receptor: an answer to its antiapoptotic action in thymus FASEB J, September 1, 1999; 13(12): 1547 - 1556. [Abstract] [Full Text]

				S.-T. J. HUANG and J. A. CIDLOWSKI Glucocorticoids inhibit serum depletion-induced apoptosis in T lymphocytes expressing Bcl-2 FASEB J, March 1, 1999; 13(3): 467 - 476. [Abstract] [Full Text]

				J. Ramdas, W. Liu, and J. M. Harmon Glucocorticoid-induced Cell Death Requires Autoinduction of Glucocorticoid Receptor Expression in Human Leukemic T Cells Cancer Res., March 1, 1999; 59(6): 1378 - 1385. [Abstract] [Full Text] [PDF]

				J. Ramdas and J. M. Harmon Glucocorticoid-Induced Apoptosis and Regulation of NF-{kappa}B Activity in Human Leukemic T Cells Endocrinology, September 1, 1998; 139(9): 3813 - 3821. [Abstract] [Full Text] [PDF]

				C. M. Pariante, B. D. Pearce, T. L. Pisell, M. J. Owens, and A. H. Miller Steroid-Independent Translocation of the Glucocorticoid Receptor by the Antidepressant Desipramine Mol. Pharmacol., October 1, 1997; 52(4): 571 - 581. [Abstract] [Full Text]

				R. H. Oakley, M. Sar, and J. A. Cidlowski The Human Glucocorticoid Receptor beta Isoform J. Biol. Chem., April 19, 1996; 271(16): 9550 - 9559. [Abstract] [Full Text] [PDF]