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Updated: Jun 20, 2026

Biochemical Reconstitution of Steroid Receptor•Hsp90 Protein Complexes and Reactivation of Ligand Binding
Published on: September 21, 2011
Identification of natural human glucocorticoid receptor (hGR) mutations or polymorphisms and their functional
Evangelia Charmandari1, George P Chrousos, Tomoshige Kino
1Division of Endocrinology and Metabolism, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
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 alpha (hGRalpha), a ligand-dependent transcription factor ubiquitously expressed in almost all tissues and cells. The molecular mechanisms of hGRalpha 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 hGRalpha 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 hGRalpha receptors would enhance our understanding of the molecular mechanisms of hGRalpha action and highlight the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology.
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