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

Research output: Chapter in Book/Report/Conference proceedingConference contribution

4 Scopus citations


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.

Original languageEnglish (US)
Title of host publicationHormonal Carcinogenesis V
EditorsJonathan Li, Sara Li, Suresh Mohla, Henri Rochefort, Henri Rochefort, Thierry Maudelonde
Number of pages7
StatePublished - 2008
Externally publishedYes

Publication series

NameAdvances in Experimental Medicine and Biology
ISSN (Print)0065-2598

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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