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Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview

The breast tissue is the site of major metabolic conversions of estradiol (E(2)) mediated by specific cytochromes P450 hydroxylations and methylation by catechol-O-methytransferase. In addition to E(2 )itself, recent findings highlight the significance of 4-hydroxylated estrogen metabolites as chemi...

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Autores principales: Guillemette, Chantal, Bélanger, Alain, Lépine, Johanie
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064083/
https://www.ncbi.nlm.nih.gov/pubmed/15535854
http://dx.doi.org/10.1186/bcr936
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author Guillemette, Chantal
Bélanger, Alain
Lépine, Johanie
author_facet Guillemette, Chantal
Bélanger, Alain
Lépine, Johanie
author_sort Guillemette, Chantal
collection PubMed
description The breast tissue is the site of major metabolic conversions of estradiol (E(2)) mediated by specific cytochromes P450 hydroxylations and methylation by catechol-O-methytransferase. In addition to E(2 )itself, recent findings highlight the significance of 4-hydroxylated estrogen metabolites as chemical mediators and their link to breast cancer development and progression, whereas, in opposition, 2-methoxylated estrogens appear to be protective. Recent data also indicate that breast tissue possesses enzymatic machinery to inactivate and eliminate E(2 )and its oxidized and methoxylated metabolites through conjugation catalyzed by UDP-glucuronosyltransferases (UGTs), which involves the covalent addition of glucuronic acid. In opposition to other metabolic pathways of estrogen, the UGT-mediated process leads to the formation of glucuronides that are devoid of biologic activity and are readily excreted from the tissue into the circulation. This review addresses the most recent findings on the identification of UGT enzymes that are responsible for the glucuronidation of E(2 )and its metabolites, and evidence regarding their potential role in breast cancer.
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spelling pubmed-10640832005-03-11 Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview Guillemette, Chantal Bélanger, Alain Lépine, Johanie Breast Cancer Res Review The breast tissue is the site of major metabolic conversions of estradiol (E(2)) mediated by specific cytochromes P450 hydroxylations and methylation by catechol-O-methytransferase. In addition to E(2 )itself, recent findings highlight the significance of 4-hydroxylated estrogen metabolites as chemical mediators and their link to breast cancer development and progression, whereas, in opposition, 2-methoxylated estrogens appear to be protective. Recent data also indicate that breast tissue possesses enzymatic machinery to inactivate and eliminate E(2 )and its oxidized and methoxylated metabolites through conjugation catalyzed by UDP-glucuronosyltransferases (UGTs), which involves the covalent addition of glucuronic acid. In opposition to other metabolic pathways of estrogen, the UGT-mediated process leads to the formation of glucuronides that are devoid of biologic activity and are readily excreted from the tissue into the circulation. This review addresses the most recent findings on the identification of UGT enzymes that are responsible for the glucuronidation of E(2 )and its metabolites, and evidence regarding their potential role in breast cancer. BioMed Central 2004 2004-09-27 /pmc/articles/PMC1064083/ /pubmed/15535854 http://dx.doi.org/10.1186/bcr936 Text en Copyright © 2004 BioMed Central Ltd
spellingShingle Review
Guillemette, Chantal
Bélanger, Alain
Lépine, Johanie
Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview
title Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview
title_full Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview
title_fullStr Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview
title_full_unstemmed Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview
title_short Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview
title_sort metabolic inactivation of estrogens in breast tissue by udp-glucuronosyltransferase enzymes: an overview
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1064083/
https://www.ncbi.nlm.nih.gov/pubmed/15535854
http://dx.doi.org/10.1186/bcr936
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