Cited by 24Pharmacogenetics and Drug MetabolismEstrogen and related hormone effectsDrug Transport and Resistance Mechanisms

Glucuronidation of estrone and 16α-hydroxyestrone by human UGT enzymes: the key roles of UGT1A10 and UGT2B7

Kallionpää, Roope A., Järvinen, Erkka, Finel, Moshe·2015·The Journal of Steroid Biochemistry and Molecular Biology

Abstract

The glucuronidation of estrone and 16α-hydroxyestrone by recombinant human UDP-glucuronosyltransferase enzymes (UGTs) of subfamilies 1A, 2A and 2B was studied. Microsomes from human liver and small intestine were also tested for the glucuronidation of these two estrogens. The results revealed that UGT1A10 is by far the most active enzyme in estrone glucuronidation. UGT1A10 also exhibited high rate of 16α-hydroxyestrone conjugation at the 3-OH, whereas UGT2B7 catalyzed its glucuronidation at high rates at the 16-OH. Human liver microsomes exhibited high rates of 16α-hydroxyestrone-16-glucuronide formation, but very low formation rates of either 16α-hydroxyestrone-3-glucuronide or estrone glucuronide. On the other hand, human intestine microsomes catalyzed the formation of all these 3 different glucuronides at high rates. Kinetic analyses revealed very low Km value for 16α-hydroxyestrone glucuronidation by UGT2B7, below 4 μM, suggesting higher affinity than commonly found among UGTs and their substrates. In further studies with UGT1A10, mutant F93G exhibited increased glucuronidation rates of 16α-hydroxyestrone, but not estrone, whereas mutations in F90 did not reveal any activity with either estrogen. Taken together, the results of this study significantly expand our understanding on the metabolism of estrogens and their interactions with the human UGTs.

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Crossref · 10.1016/j.jsbmb.2015.07.013

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Authors
Kallionpää, R. A., Järvinen, E., & Finel, M.
Affiliations
University of Helsinki (FI)
Corresponding author
Finel, Moshe
Venue
The Journal of Steroid Biochemistry and Molecular Biology
Publisher
Elsevier BV
Published
2015-11
Volume
154
Pages
104-111
ISSN
0960-0760 (ISSN-L)
OpenAlex
W1033823202
Cited by
24
References
35
Citations by year
2026: 3 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 2
FWCI
4.67
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Steroid Biochemistry and Molecular Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Academy of Finland (12600101)
  • Sigrid Juselius Foundation (47033421)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
Keywords
glucuronidation, estrone, 16α-hydroxyestrone, UDP-glucuronosyltransferase, UGT1A10, UGT2B7, estrogen metabolism, liver microsomes, intestinal microsomes, enzyme kinetics, glucuronide formation
MeSH terms
Estrone, Hydroxyestrones, Intestines, Kinetics, Microsomes, Liver, Substrate Specificity, Glucuronosyltransferase, Glucuronides

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