Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • 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
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
  • Log out
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

GLUCURONIDATION OF ANABOLIC ANDROGENIC STEROIDS BY RECOMBINANT HUMAN UDP-GLUCURONOSYLTRANSFERASES

Tiia Kuuranne, Mika Kurkela, Mario Thevis, Wilhelm Schänzer, Moshe Finel and Risto Kostiainen
Drug Metabolism and Disposition September 2003, 31 (9) 1117-1124; DOI: https://doi.org/10.1124/dmd.31.9.1117
Tiia Kuuranne
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mika Kurkela
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mario Thevis
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wilhelm Schänzer
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Moshe Finel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Risto Kostiainen
  • 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

A multidimensional study on the glucuronidation of anabolic androgenic steroids and their phase I metabolites by 11 recombinant human UDP-glucuronosyltransferases (UGTs) was carried out using liquid chromatographic-tandem mass spectrometric analyses. Large differences between the enzymes with respect to the conjugation profiles of the 11 tested aglycones were detected. Two UGTs, 1A6 and 1A7, did not exhibit measurable activity toward any of the aglycones that were examined in this study. Regioselectivity was demonstrated by UGTs 1A8, 1A9, and 2B15 that preferentially catalyzed hydroxyl glucuronidation at the 17β-position. Most of the other enzymes glucuronidated hydroxyl groups at both the 3α- and the 17β-positions. Clear stereoselectivity was observed in glucuronidation of diastereomeric nandrolone metabolites (5α-estran-3α-ol-17-one and 5β-estran-3α-ol-17-one), whereas such specificity was not seen when analogous methyltestosterone metabolites were assayed. UGTs 1A1, 1A3, 1A4, 1A8, 1A9, 1A10, 2B4, 2B7, and 2B15 readily glucuronidated 5α-androstane-3α,17β-diol, but none of them exhibited methyltestosterone glucuronidation activity. In agreement with the latter observations, we found that the methyltestosterone glucuronidation activity of human liver microsomes is extremely low, whereas in induced rat liver microsomes it was significantly higher. The homology among UGTs 1A7 to 1A10 at the level of amino acid sequence is very high, and it was thus surprising to find large differences in their activity toward this set of aglycones. Furthermore, the high activity of UGT1A8 and 1A10 toward some of the substrates indicates that extrahepatic enzymes might play a role in the metabolism of anabolic androgenic steroids.

Footnotes

  • ↵1 Abbreviations used are: UGT(s), UDP-glucuronosyltransferase(s); LC-MS/MS, liquid chromatography-tandem mass spectrometry; UDPGA, UDP-glucuronic acid; DMSO, dimethyl sulfoxide; SPE, solid phase extraction; TES, testosterone; NAN, nandrolone; MT, methyltestosterone; 5β-EPIM, 17β-methyl-5β-androst-4-ene-3α,17α-diol; 5α-A, 5α-androstane-3α,17β-diol; 5α-N, 5α-estran-3α-ol-17-one; 5β-N, 5β-estran-3α-ol-17-one; 5α-1-ME, 1-methyl-5α-androst-1-en-17β-ol-3-one.

  • This work was supported by European Union Grant G6RD-CT-2001-00513, the National Technology Agency (TEKES, Grant 45090308), and University Pharmacy (personal grant to T.K.).

    • Received March 19, 2003.
    • Accepted June 12, 2003.
  • 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: 31 (9)
Drug Metabolism and Disposition
Vol. 31, Issue 9
1 Sep 2003
  • 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 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.
GLUCURONIDATION OF ANABOLIC ANDROGENIC STEROIDS BY RECOMBINANT HUMAN UDP-GLUCURONOSYLTRANSFERASES
(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

GLUCURONIDATION OF ANABOLIC ANDROGENIC STEROIDS BY RECOMBINANT HUMAN UDP-GLUCURONOSYLTRANSFERASES

Tiia Kuuranne, Mika Kurkela, Mario Thevis, Wilhelm Schänzer, Moshe Finel and Risto Kostiainen
Drug Metabolism and Disposition September 1, 2003, 31 (9) 1117-1124; DOI: https://doi.org/10.1124/dmd.31.9.1117

Citation Manager Formats

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

Share
Research ArticleArticle

GLUCURONIDATION OF ANABOLIC ANDROGENIC STEROIDS BY RECOMBINANT HUMAN UDP-GLUCURONOSYLTRANSFERASES

Tiia Kuuranne, Mika Kurkela, Mario Thevis, Wilhelm Schänzer, Moshe Finel and Risto Kostiainen
Drug Metabolism and Disposition September 1, 2003, 31 (9) 1117-1124; DOI: https://doi.org/10.1124/dmd.31.9.1117
del.icio.us logo Digg logo Reddit logo Twitter 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

  • Determination of Acyl-, O-, and N-Glucuronide
  • TMDD Affects PK of IL-10 Fc-fusion Proteins
  • Uptake as the RDS in Pevonedistat Hepatic Clearance
Show more Articles

Similar Articles

Advertisement
  • 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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics