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Molecular Mechanisms of Regulation of Gene Expression by Glucocorticoids

  • Conference paper
Book cover Recombinant DNA Technologies in Neuroendocrinology

Part of the book series: Current Topics in Neuroendocrinology ((CT NEUROENDOCRI,volume 11))

  • 43 Accesses

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.

This work was supported by grants from the Swedish Medical Research Council (No. 13X-2819), the Swedish Cancer Society, the Magnus Bergvall Foundation and the Swedish Society of Medical Research.

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  1. Department of Medical Nutrition, Karolinska Institute, Huddinge University Hospital F60, NOVUM, S-141 86, Huddinge, Sweden

    J.-Å. Gustafsson

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  1. Y. Dong
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  2. S. Okret
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  3. J.-Å. Gustafsson
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  1. Dept. of Internal Medicine, Kyoto University, Faculty of Medicine, 54 Kawaharacho, Shogoin, Sakyo-ku Kyoto 606, Japan

    Hiroo Imura M. D. (Professor) (Professor)

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Dong, Y., Okret, S., Gustafsson, JÅ. (1993). Molecular Mechanisms of Regulation of Gene Expression by Glucocorticoids. In: Imura, H. (eds) Recombinant DNA Technologies in Neuroendocrinology. Current Topics in Neuroendocrinology, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-77503-1_2

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  • DOI: https://doi.org/10.1007/978-3-642-77503-1_2

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