Molecular mechanisms regulating glucocorticoid sensitivity and resistance

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 o...

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Bibliographic Details
Published in:Molecular and cellular endocrinology 2009-03, Vol.300 (1-2), p.7-16
Main Authors: Gross, Katherine L., Lu, Nick Z., Cidlowski, John A.
Format: Article
Language:English
Subjects:
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Gene Expression Regulation
Glucocorticoid receptor
Glucocorticoid resistance
Glucocorticoids - metabolism
Hematological malignancy
Humans
Polymorphism, Genetic
Protein Isoforms - genetics
Protein Isoforms - metabolism
Receptors, Glucocorticoid - agonists
Receptors, Glucocorticoid - genetics
Receptors, Glucocorticoid - metabolism
Signal Transduction - physiology
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Summary: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.
ISSN:0303-7207
1872-8057
DOI:10.1016/j.mce.2008.10.001