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Identification of Natural Human Glucocorticoid Receptor (hGR) Mutations or Polymorphisms and Their Functional Consequences at the Hormone–Receptor Interaction Level

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Molecular Endocrinology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 590))

Abstract

Glucocorticoids regulate a broad spectrum of physiologic functions essential for life and play an important role in the maintenance of basal and stress-related homeostasis. At the cellular level, the actions of glucocorticoids are mediated by the human glucocorticoid receptor α (hGRα), a ligand-dependent transcription factor ubiquitously expressed in almost all tissues and cells. The molecular mechanisms of hGRα action involve (a) binding to glucocorticoids, (b) cytoplasmic to nuclear translocation, (c) binding/association to DNA/chromatin, and (d) transcriptional activation or repression by interacting with cofactors and other transcription factors. Mutations or polymorphisms in the hGR gene may impair these molecular mechanisms of hGRα action, thereby altering tissue sensitivity to glucocorticoids. The latter may take the form of glucocorticoid resistance or glucocorticoid hypersensitivity and may be associated with significant morbidity. The identification of natural pathologic mutations in patients’ hGR gene and the subsequent examination of the functional defects of the natural mutant hGRα receptors would enhance our understanding of the molecular mechanisms of hGRα action and highlight the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology.

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Acknowledgements

This book chapter was created based on the work supported in part by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

Author information

Authors and Affiliations

  1. Division of Endocrinology and Metabolism, Section on Pediatric Endocrinology, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

    Evangelia Charmandari

  2. Department of Pediatrics, Athens University Medical School, Athens, Greece

    George P. Chrousos

  3. Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA

    Tomoshige Kino

Authors
  1. Evangelia Charmandari
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  2. George P. Chrousos
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  3. Tomoshige Kino
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Editor information

Editors and Affiliations

  1. College of Medicine, University of Kentucky, Rose Street 800, Lexington, 40536-0298, U.S.A.

    Ok-Kyong Park-Sarge

  2. Dept. Obstetrics & Gynecology, University of Kentucky, Rose Street 800, Lexington, 40536-0293, U.S.A.

    Thomas E. Curry

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Charmandari, E., Chrousos, G.P., Kino, T. (2009). Identification of Natural Human Glucocorticoid Receptor (hGR) Mutations or Polymorphisms and Their Functional Consequences at the Hormone–Receptor Interaction Level. In: Park-Sarge, OK., Curry, T. (eds) Molecular Endocrinology. Methods in Molecular Biology, vol 590. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60327-378-7_3

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  • DOI: https://doi.org/10.1007/978-1-60327-378-7_3

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-60327-377-0

  • Online ISBN: 978-1-60327-378-7

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