title: Molecular mechanisms regulating glucocorticoid sensitivity and resistance.
abstract: Glucocorticoid receptor agonists are mainstays in the treatment of various malignancies of hematological origin. Glucocorticoids are included in therapeutic regimens for their ability to stimulate intracellular signal transduction cascades that culminate in alterations in the rate of transcription of genes involved in cell cycle progression and programmed cell death. Unfortunately, subpopulations of patients undergoing systemic glucocorticoid therapy for these diseases are or become insensitive to glucocorticoid-induced cell death, a phenomenon recognized as glucocorticoid resistance. Multiple factors contributing to glucocorticoid resistance have been identified. Here we summarize several of these mechanisms and describe the processes involved in generating a host of glucocorticoid receptor isoforms from one gene. The potential role of glucocorticoid receptor isoforms in determining cellular responsiveness to glucocorticoids is emphasized.
authors.affiliation: Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Gross
authors.forename: Nick Z
authors.initials: NZ
authors.lastname: Lu
authors.forename: John A
authors.initials: JA
authors.lastname: Cidlowski
mesh_terms: D005786:Gene Expression Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005938:Glucocorticoids; D020033:Protein Isoforms; D011965:Receptors, Glucocorticoid