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
  • Log out
  • 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
  • Log out
  • 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

Modification of OATP2B1-Mediated Transport by Steroid Hormones

Markus Grube, Kathleen Köck, Susanne Karner, Sebastian Reuther, Christoph A. Ritter, Gabriele Jedlitschky and Heyo K. Kroemer
Molecular Pharmacology November 2006, 70 (5) 1735-1741; DOI: https://doi.org/10.1124/mol.106.026450
Markus Grube
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kathleen Köck
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susanne Karner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sebastian Reuther
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Christoph A. Ritter
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gabriele Jedlitschky
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heyo K. Kroemer
  • 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

The family of the organic anion transporting polypeptides forms an increasing group of uptake transport proteins with a wide substrate spectrum. Although the expression of some members of this group, such as organic anion transporting polypeptide (OATP)-A or C, is limited to special tissues (such as liver or brain), the organic anion transporting polypeptide 2B1 (OATPB/SLCO2B1) is expressed in many organs, including liver, placenta, mammary gland, brain, and intestine. However, little is known about its function in those tissues because only a limited number of compounds, such as dehydroepiandrosterone-sulfate (DHEAS) and estrone-3-sulfate (E3S), have been characterized as OATP2B1 substrates. To further elucidate the role of OATP2B1 on steroid transport, we examined the influence of steroid hormones on OATP2B1-mediated E3S and DHEAS uptake using OATP2B1-overexpressing Madin-Darby canine kidney II cells. We identified unconjugated androgens (e.g., testosterone) as potent inhibitors for OATP2B1. In contrast, gestagenes such as progesterone enhanced E3S uptake in a concentration-dependent manner to up to 300% of the control, accompanied by a significant decrease in the OATP2B1 Km value for E3S (control, Km = 14 μM; in the presence of 31.6 μM progesterone, Km = 3.6 μM). Moreover, we demonstrated that testosterone and progesterone are not substrates of OATP2B1, indicating an allosteric mechanism for the observed effects. Furthermore, we showed that progesterone enhances the OATP2B1-dependent pregnenolone sulfate transport. Taken together, the results indicate functional modification of OATP2B1-mediated E3S and DHEAS as well as pregnenolone sulfate transport through steroid hormones such as progesterone. These effects can have physiological consequences for the organ-specific uptake of steroids.

Footnotes

  • This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB/TR 19-04), the Deutsche Krebshiffe (grant 502735), and the German Federal Ministry of Education and Research (NBL3 program, reference 01 ZZ 0103).

  • M.G. and K.K. contributed equally to this work.

  • ABBREVIATIONS: OATP, organic anionic polypeptide transporter; E3S, estrone-3-sulfate; DHEAS, dehydroepiandrosterone-sulfate; MDCK, Madin-Darby canine kidney; DMSO, dimethyl sulfoxide; P-gp, P-glycoprotein.

    • Received May 8, 2006.
    • Accepted August 14, 2006.
  • 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: 70 (5)
Molecular Pharmacology
Vol. 70, Issue 5
1 Nov 2006
  • 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 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.
Modification of OATP2B1-Mediated Transport by Steroid Hormones
(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

Modification of OATP2B1-Mediated Transport by Steroid Hormones

Markus Grube, Kathleen Köck, Susanne Karner, Sebastian Reuther, Christoph A. Ritter, Gabriele Jedlitschky and Heyo K. Kroemer
Molecular Pharmacology November 1, 2006, 70 (5) 1735-1741; DOI: https://doi.org/10.1124/mol.106.026450

Citation Manager Formats

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

Modification of OATP2B1-Mediated Transport by Steroid Hormones

Markus Grube, Kathleen Köck, Susanne Karner, Sebastian Reuther, Christoph A. Ritter, Gabriele Jedlitschky and Heyo K. Kroemer
Molecular Pharmacology November 1, 2006, 70 (5) 1735-1741; DOI: https://doi.org/10.1124/mol.106.026450
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

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