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Estrogenic Activity of the Equine Estrogen Metabolite, 4-Methoxyequilenin

  • Minsun Chang
  • Cassia R. Overk
  • Irida Kastrati
  • Kuan-wei Peng
  • Ping Yao
  • Zhi-Hui Qin
  • Pavel Petukhov
  • Judy L. Bolton
  • Gregory R. J. Thatcher
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 617)

Summary

Oxidative metabolism of estrogens has been associated with genotoxicity.O-methylation of catechol estrogens is considered as a protective mechanism.4-Methoxyequilenin (4-MeOEN) is the O-methylated product of 4-hydroxyequilenin(4-OHEN). 4-OHEN, the major catechol metabolite of the equine estrogens present inthe most widely prescribed hormone replacement therapeutics, causes DNA damagevia quinone formation. In this study, estrogen receptor (ERα) binding of 4-MeOENwas compared with estradiol (E2) and equilenin derivatives including 4-BrEN usingcomputer modeling, estrogen response element (ERE)-luciferase induction in MCF-7cells, and alkaline phosphatase (AP) induction in Ishikawa cells. 4-MeOEN inducedAP and luciferase with nanomolar potency and displayed a similar profile of activityto E2. Molecular modeling indicated that MeOEN could be a ligand for ERα despiteno binding being observed in the ERα competitive binding assay. Methylationof 4-OHEN may not represent a detoxification pathway, since 4-MeOEN is a fullestrogen agonist with nanomolar potency.

Keywords

Estrogenic Activity Ligand Binding Domain Estrogen Response Element Ishikawa Cell Catechol Estrogen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer 2008

Authors and Affiliations

  • Minsun Chang
  • Cassia R. Overk
  • Irida Kastrati
  • Kuan-wei Peng
  • Ping Yao
  • Zhi-Hui Qin
  • Pavel Petukhov
  • Judy L. Bolton
  • Gregory R. J. Thatcher
    • 1
  1. 1.Department of Medicinal Chemistry and Pharmacology College of PharmacyUniversity of IllinoisChicagoUSA

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