Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Dexamethasone Induction of Murine CYP2B Genes Requires the Glucocorticoid Receptor

Étienne Audet-Walsh and Alan Anderson
Drug Metabolism and Disposition March 2009, 37 (3) 580-588; DOI: https://doi.org/10.1124/dmd.108.022772
Étienne Audet-Walsh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alan Anderson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Hepatic cytochrome P450 (P450) enzymes metabolize exogenous and endogenous compounds, and many are inducible by xenobiotics. Their synthesis is tightly regulated, particularly through nuclear receptors. Expression of murine CYP2B genes is strongly activated by treatment with phenobarbital or phenobarbital-like inducers, and a detectable response requires the presence of the constitutive androstane receptor (CAR). However, other compounds can also induce murine CYP2B proteins. For example, dexamethasone is known to induce rat CYP2B1 and CYP2B2 and mouse CYP2B10. Using human HepG2 and rat H4IIEC3 hepatoma cell lines, we found that dexamethasone induction of CYP2B2 and Cyp2b10 luciferase reporters required the glucocorticoid receptor. Given the well known observation that CYP2B genes are not phenobarbital-responsive in cultured cell lines, the dexamethasone responsiveness of CYP2B reporter constructs in cell lines demonstrates in itself that the mechanism of dexamethasone induction is distinct from that of phenobarbital. We also analyzed the relative importance of the phenobarbital response unit (PBRU) and of a known glucocorticoid response element in this response. Both sites contributed to the response, but other sites were required for maximal induction. CAR was also found to act as an accessory factor to stimulate the response to dexamethasone by the glucocorticoid receptor. Furthermore, in H4IIEC3 cells, CAR activated the PBRU in the natural sequence context of the CYP2B2 and Cyp2b10 5′ flanks. In summary, there are at least two independent mechanisms of CYP2B induction: one involving phenobarbital and phenobarbital-like inducers and another involving glucocorticoids that induce via the glucocorticoid receptor with CAR acting as an accessory factor.

Footnotes

  • This work was supported by the Instituts de Recherche en Santé du Canada [Grant 77580].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.022772.

  • ABBREVIATIONS: PB, phenobarbital; PBRU, phenobarbital response unit; bp, base pair; CAR, constitutive androstane receptor; PBREM, phenobarbital responsive enhancer module; NF, nuclear factor; PXR, pregnane X receptor; DEX, dexamethasone; GR, glucocorticoid receptor; GRE, glucocorticoid response element; GRU, glucocorticoid response unit; PEPCK, phosphoenolpyruvate carboxykinase; kb, kilobase; DMSO, dimethyl sulfoxide; FBS, fetal bovine serum; RU486, 17β-hydroxy-11β-[4-dimethylamino phenyl]-17α-[1-propynyl]estra-4,9-dien-3-one.

    • Received June 10, 2008.
    • Accepted November 24, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 37 (3)
Drug Metabolism and Disposition
Vol. 37, Issue 3
1 Mar 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Dexamethasone Induction of Murine CYP2B Genes Requires the Glucocorticoid Receptor
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Dexamethasone Induction of Murine CYP2B Genes Requires the Glucocorticoid Receptor

Étienne Audet-Walsh and Alan Anderson
Drug Metabolism and Disposition March 1, 2009, 37 (3) 580-588; DOI: https://doi.org/10.1124/dmd.108.022772

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

Dexamethasone Induction of Murine CYP2B Genes Requires the Glucocorticoid Receptor

Étienne Audet-Walsh and Alan Anderson
Drug Metabolism and Disposition March 1, 2009, 37 (3) 580-588; DOI: https://doi.org/10.1124/dmd.108.022772
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Candesartan glucuronide serves as a CYP2C8 inhibitor
  • Role of AADAC on eslicarbazepine acetate hydrolysis
  • Gene expression profile of human intestinal epithelial cells
Show more Articles

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics