An immunocytochemical procedure for the human glucocorticoid receptor (GR) was developed herein in order to assess its level and subcellular distribution in a well-studied system of childhood acute lymphoblastic leukemia cells (CEM), in which sensitive and resistant subclones have been established, and in different tissue preparations (lymph node biopsies, bone marrow aspirates and peripheral blood) from patients with various forms of leukemia or lymphoma. In the absence of preincubation with steroid, the GR was localized predominantly in the cell cytoplasm and to a weaker extent in the nucleus of CEM cells. Following incubation with glucocorticoid, an increase in nuclear GR was observed in the steroid-sensitive CEM-C7 and C7E$ sb2$A cell lines but not in the resistant C7 subclones (4R4, 3R43 and ICR27). Incubation of human peripheral mononuclear cells with 10$ sp{-6}$M dexamethasone for 30 or 60 minutes in vitro resulted in a marked increase in nuclear GR immunoreactivity. Since nuclear translocation of GR is a critical step in glucocorticoid hormone action on target cells, assessment of the subcellular distribution of GR may provide functional tests for steroid responsiveness. Furthermore, the effect of glucocorticoids on the regulation of GR and its mRNA was studied by immunocytochemistry, RIA and in situ hybridization.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.59525 |
| Date | January 1989 |
| Creators | O'Donnell, Dajan J. (Dajan James) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Anatomy.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001069302, proquestno: AAIMM63653, Theses scanned by UMI/ProQuest. |
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