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Endocrinology Vol. 138, No. 11 5028-5038
Copyright © 1997 by The Endocrine Society

ARTICLES

Expression and Subcellular Distribution of the ß-Isoform of the Human Glucocorticoid Receptor1

Robert H. Oakley2, Jeffrey C. Webster, Madhabananda Sar, C. Richard Parker, Jr. and John A. Cidlowski

Laboratory of Signal Transduction (R.H.O., J.C.W., M.S., J.A.C.), National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709; and the Department of Obstetrics and Gynecology, University of Alabama (C.R.P.), Birmingham, Alabama 35233

Address all correspondence and requests for reprints to: Dr. John A. Cidlowski, Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, P.O. Box 12233, MD E2–02, Research Triangle Park, North Carolina 27709. E-mail: cidlowski{at}niehs.nih.gov

Alternative splicing of the human glucocorticoid receptor (hGR) primary transcript produces two highly homologous protein isoforms, termed hGR{alpha} and hGRß, that differ at their carboxy-termini. In contrast to the well characterized hGR{alpha} isoform, which modulates gene expression in a hormone-dependent fashion, the biological significance of hGRß has only recently begun to emerge. We and others have shown that the hGRß messenger RNA transcript is widely expressed in human tissues and that the hGRß protein functions as a dominant negative inhibitor of hGR{alpha} in transfected cells. Unfortunately, these initial studies did not determine whether the hGRß protein was made in vivo. Such analyses are hindered because available anti-hGR antibodies cannot discriminate between the similarly sized hGR{alpha} and hGRß proteins. Therefore, to investigate the expression of the hGRß protein, we have produced an antipeptide, hGRß-specific antibody termed BShGR. This antibody was made against the unique 15-amino acid peptide at the carboxy-terminus of hGRß and recognizes both the native and denatured conformations of hGRß, but does not cross-react with hGR{alpha}. Using BShGR on Western blots and in immunoprecipitation experiments, we detected the hGRß protein in a variety of human cell lines and tissues. Immunocytochemistry was then performed with BShGR on HeLa S3 and CEM-C7 cells and on tissue sections prepared from lung, thymus, and liver to assess the cellular and subcellular distribution of hGRß. In all immunopositive cells, hGRß was found in the nucleus independent of glucocorticoid treatment. Within tissues, the hGRß protein was expressed most abundantly in the epithelial cells lining the terminal bronchiole of the lung, forming the outer layer of Hassall’s corpuscle in the thymus, and lining the bile duct in the liver. As a potential in vivo inhibitor of hGR{alpha} activity, expression of hGRß may be an important factor regulating target cell responsiveness to glucocorticoids.




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