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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Beneficial Effects of a Novel Thyromimetic on Lipoprotein Metabolism

Anthony H. Taylor, Zouhair F. Stephan, Ronald E. Steele and Norman C. W. Wong
Molecular Pharmacology September 1997, 52 (3) 542-547; DOI: https://doi.org/10.1124/mol.52.3.542
Anthony H. Taylor
Endocrine Research Group, Departments of Medicine and Medical Biochemistry, the Faculty of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada, 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zouhair F. Stephan
Endocrine Research Group, Departments of Medicine and Medical Biochemistry, the Faculty of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada, 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ronald E. Steele
Endocrine Research Group, Departments of Medicine and Medical Biochemistry, the Faculty of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada, 1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Norman C. W. Wong
Endocrine Research Group, Departments of Medicine and Medical Biochemistry, the Faculty of Medicine, University of Calgary, Health Sciences Centre, Calgary, Alberta, Canada, 1 2
  • 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

Although l-triiodothyronine (l-T3) lowers cholesterol, this hormone is not used to treat hypercholesterolemia because of its cardiotoxic effects. Thyromimetics, such as the novel compound CGS 23425, that mimic the beneficial but lack the detrimental effects of T3, may be useful in the treatment of hypercholesterolemia. To show that CGS 23425 has no cardiotoxicity, atrial contractility and force were both measured and found to be unchanged in rats treated with up to 10 mg/kg drug. The lipid lowering actions of this drug resulted in a 44% decrease in low-density lipoprotein (LDL) cholesterol in hypercholesterolemic rats treated with 10 μg/kg of the compound. Normal rats required a higher dose of 1000 μg/kg to elicit a similar 50% reduction in LDL cholesterol. Both CGS 23425 or T3 (10 nm) increased the specific binding of 125I-labeled LDL to Hep G2 cells and increased LDL receptor number by 44 and 49%, respectively. These data indicate that CGS 23425 enhances hepatic clearance of serum LDL cholesterol. Normal and fat-fed animals treated with the drug showed a dose-dependent increase in apolipoprotein AI, a protein that promotes the efflux of cholesterol from peripheral tissues. Transient transfection of a rat apolipoprotein AI promoter-chloramphenicol acetyltransferase construct, in human hepatoma cells, showed a dose-dependent increase in chloramphenicol acetyltransferase activity with EC50 values of 2 × 10-12 m and 10-10 m for thyroid hormone receptors β1 and α1, respectively, with maximal responses at 10-7 m. These data indicate that CGS 23425 is a thyromimetic that increases apolipoprotein AI expression via thyroid hormone receptor. In summary, CGS 23425 ameliorates hypercholesterolemia by increasing apolipoprotein A1 and the clearance of LDL cholesterol. Therefore, a compound like CGS 23425 may be useful for the prevention and reversal of atherosclerosis.

Footnotes

    • Received March 10, 1997.
    • Accepted May 15, 1997.
  • Send reprint requests to: Dr. N. C. W. Wong, University of Calgary, Depts. of Medicine and Medical Biochemistry, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1 Canada. E-mail:ncwwong{at}acs.ucalgary.ca

  • Funding for a portion of this project was provided by the Medical Research Council of Canada and the Heart and Stroke Foundation of Canada. N.C.W.W. is a recipient of a Senior Scholarship Award from the Alberta Heritage Foundation for Medical Research and a Scientist Award from the Medical Research Council.

  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm 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

Molecular Pharmacology: 52 (3)
Molecular Pharmacology
Vol. 52, Issue 3
1 Sep 1997
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology 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.
Beneficial Effects of a Novel Thyromimetic on Lipoprotein Metabolism
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Beneficial Effects of a Novel Thyromimetic on Lipoprotein Metabolism

Anthony H. Taylor, Zouhair F. Stephan, Ronald E. Steele and Norman C. W. Wong
Molecular Pharmacology September 1, 1997, 52 (3) 542-547; DOI: https://doi.org/10.1124/mol.52.3.542

Citation Manager Formats

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

Beneficial Effects of a Novel Thyromimetic on Lipoprotein Metabolism

Anthony H. Taylor, Zouhair F. Stephan, Ronald E. Steele and Norman C. W. Wong
Molecular Pharmacology September 1, 1997, 52 (3) 542-547; DOI: https://doi.org/10.1124/mol.52.3.542
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 and Discussion
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of Celecoxib targets by label-free TPP
  • Editing TOP2α Intron 19 5′ SS Circumvents Drug Resistance
  • CTS Bias
Show more Article

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

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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