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Mechanisms of Glucocorticoid Hormone Action

  • Emily P. Slater
  • Thomas Anderson
  • Peter Cattini
  • Randi Isaacs
  • Morris J. Birnbaum
  • David G. Gardner
  • Norman L. Eberhardt
  • John D. Baxter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 196)

Abstract

This report summarizes our studies, in context with the results of other laboratories, of the molecular mechanisms of glucocorticoid hormone action. The receptors for these steroids are comprised of single polypeptide chains of about 90,000 molecular weight. Binding of agonist steroids to the receptor induces a conformational change to an active receptor form that is followed by a second change in the glucocorticoid-receptor complex, termed activation, that alters the charge of the complex and results in its binding to specific sites on the DNA termed glucocorticoid regulatory elements (GREs). The GRE on the human metallothionein-IIA gene is located in the 5′-flanking DNA. It can function independently of the gene’s promoter, and when ligated upstream from the herpes simplex virus (HSV) thymidine kinase (TK) gene promoter, can activate it. The binding of the glucocorticoidreceptor complex to the GRE probably alters chromatin structure over a limited span to facilitate RNA polymerase action. The regulation by glucocorticoids of growth hormone gene expression is more complex. The steroid appears to elicit both transcriptional and post-transcriptional influences that are also affected by thyroid hormone. Also the glucocorticoid influences appear to be exerted in part through DNA structures located downstream from the transcriptional initiation site. A GRE has been defined in intron A of the hGH gene through gene transfer and DNA binding experiments. Finally, gene transfer experiments suggest that pituitary-specific factors influence the ability of glucocorticoids to affect GH gene expression.

Keywords

Glucocorticoid Receptor Thymidine Kinase Mouse Mammary Tumor Virus Growth Hormone Gene Glucocorticoid Hormone 
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

© Plenum Press, New York 1986

Authors and Affiliations

  • Emily P. Slater
    • 1
  • Thomas Anderson
    • 1
  • Peter Cattini
    • 1
  • Randi Isaacs
    • 1
  • Morris J. Birnbaum
    • 1
  • David G. Gardner
    • 1
  • Norman L. Eberhardt
    • 1
  • John D. Baxter
    • 1
  1. 1.Departments of Medicine, Biochemistry and Biophysics and the Metabolic Research Unit671 HSE, University of CaliforniaSan FranciscoUSA

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