DMD

Home Help [Feedback] [For Subscribers] [Archive] [Search] --
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on October 1, 2007; DOI: 10.1124/dmd.107.018184

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.107.018184v1
36/1/51    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kato, Y.
Right arrow Articles by Degawa, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kato, Y.
Right arrow Articles by Degawa, M.


Received for publication August 9, 2007.
Revised September 26, 2007.
Accepted for publication September 27, 2007.

Hepatic UDP-Glucuronosyltransferases Responsible for Glucuronidation of Thyroxine T4 in Humans

Yoshihisa Kato 1*, Shin-ichi Ikushiro 2, Yoshikazu Emi 3, Sekihiro Tamaki 4, Hiroshi Suzuki 4, Toshiyuki Sakaki 2, Shizuo Yamada 4, Masakuni Degawa 4

1 Tokushima Bunri University 2 Toyama Prefectural University 3 University of Hyogo 4 University of Shizuoka

* Address correspondence to: E-mail: kato{at}kph.bunri-u.ac.jp

Abstract

To clarify the UDP-glucuronosyltransferase (UGT) isoform(s) responsible for the glucuronidation of thyroid hormone thyroxine T4 (T4) in the human liver, the T4-glucuronidation activities of recombinant human UGT isoforms and 7 individual human liver microsomes were comparatively examined. Among the 12 recombinant human UGT1A and UGT2B subfamily enzymes examined, UGT1A1, UGT1A3, UGT1A9 and UGT1A10 showed definite activities for T4-glucuronidation. These UGT1A enzymes, with an exception of UGT1A10, were detected in all the human liver microsomes examined. Interindividual difference in T4-glucuronidation activity was observed among the 7 individual human liver microsomes, and the T4-glucuronidation activity was closely correlated with {beta}-estradiol 3-glucuronidation activity. Furthermore, Spearman correlation analysis for a relationship between the T4-glucuronidation activity and the level of UGT1A1, UGT1A3, or UGT1A9 in the microsomes revealed that levels of UGT1A1 and UGT1A3, but not UGT1A9, were closely correlated with T4-glucuronidation activity. T4-glucuronidation activity in human liver microsomes was strongly inhibited by 26,26,26,27,27,27-hexafluoro-1{alpha},23(S),25-trihydroxyvitamin D3 (an inhibitor of UGT1A3), moderately by either bilirubin (an inhibitor of UGT1A1) or {beta}-estradiol (an inhibitor of UGT1A1 and UGT1A9), but not by propofol (an inhibitor of UGT1A9). These findings strongly indicated that glucuronidation of T4 in the human liver was mediated by UGT1A subfamily enzymes, especially UGT1Al and UGT1A3, and further suggested that the interindividual difference would come from that in the expression levels of UGT1A1 and UGT1A3 in individual human livers.


Key words: glucuronidation, hormonal regulation, UDP glucuronyltransferases


This article has been cited by other articles:


Home page
 Drug Metab. Dispos.Home page
J. Guo, A. Liu, H. Cao, Y. Luo, J. M. Pezzuto, and R. B. van Breemen
Biotransformation of the Chemopreventive Agent 2',4',4-Trihydroxychalcone (Isoliquiritigenin) by UDP-Glucuronosyltransferases
Drug Metab. Dispos., October 1, 2008; 36(10): 2104 - 2112.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] --
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics.