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Molecular Mechanisms of Regulation of Gene Expression by Glucocorticoids

  • Y. Dong
  • S. Okret
  • J.-Å. Gustafsson
Conference paper
Part of the Current Topics in Neuroendocrinology book series (CT NEUROENDOCRI, volume 11)

Abstract

The current model of glucocorticoid hormone action is summarized in Fig. 1. After synthesis, glucocorticoids are secreted into the blood stream and transported to target cells where they bind with high affinity (K d~10−9 M) and specificity to the intracellular glucocorticoid receptor (GR) protein. The sub-cellular localization of hormone-free GR is still a controversial issue. However, most data support the idea that unliganded GR is in the cytoplasmic compartment or loosely associated with the nucleus (Picard and Yamamoto 1987; Gustafsson et al. 1987 and references therein; LaFond et al. 1988; Gasc et al. 1989). Upon ligand binding, GR is activated into a form capable of interacting with DNA. The mechanism of GR activation probably involves a conformational change and dissociation from nonreceptor components, e.g., the 90-kDA heat shock protein (hsp90:Pratt et al. 1988; Bresnick et al. 1989; Denis and Gustafsson 1989). The subcellular location of activated GR has been firmly established to be inside the nucleus. In vivo, the hormone-receptor complex interacts with specific DNA sequences, termed glucocorticoid responsive element (GRE; see below and Becker et al. 1986), and elicits transcriptional activation or inhibition of target gene expression (reviewed in Yamamoto 1985) by a largely unknown mechanism. It is clear that GR is a central element in glucocorticoid hormone action and a defect at any step through the signal transduction pathway will cause glucocorticoid resistance.

Keywords

Glucocorticoid Receptor Mouse Mammary Tumor Virus Glucocorticoid Hormone Glucocorticoid Response Element Heterologous Promoter 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • Y. Dong
  • S. Okret
  • J.-Å. Gustafsson
    • 1
  1. 1.Department of Medical Nutrition, Karolinska InstituteHuddinge University Hospital F60HuddingeSweden

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