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Demonstration of the Intracellular Localization and Up-Regulation of Glucocorticoid Receptor by in Situ Hybridization and Immunocytochemistry¹

Department of Anatomy, McGill University, Montreal, Quebec, H3A 2B2, Canada [T. A., D. O.], and Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas [E. B. T.]

Glucocorticoid response in target cells closely correlates with glucocorticoid receptor (GR) level. We have compared the localization of GR (by immunocytochemimstry) and GR mRNA levels (by in situ hybridization) in steroid-sensitive and steroid-resistant subclones derived from the human CEM lymphoid cell line. In addition, GR was localized in lymphoid cells from patients with various hematological malignancies. In the absence of preincubation with the steroid, GR was localized at the light and electron microscopic level predominantly in the cytoplasm and to a weaker extent in the nucleus. In the presence of steroid, the GR was shown to translocate to the nucleus in the steroid-sensitive but not in the steroid-resistant cell lines. Furthermore, GR and GR mRNA levels were increased following glucocorticoid treatment of the sensitive cell line but not the resistant one. These data support a role for receptor regulation and translocation in the overall mechanism of glucocorticoid hormone action.