TY - JOUR
T1 - Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells
AU - Gong, Ping
AU - Madak-Erdogan, Zeynep
AU - Flaws, Jodi A.
AU - Shapiro, David J.
AU - Katzenellenbogen, John A.
AU - Katzenellenbogen, Benita S.
N1 - Publisher Copyright:
© 2016 Elsevier Ireland Ltd
PY - 2016/12/5
Y1 - 2016/12/5
N2 - Botanical estrogen (BE) dietary supplements are consumed by women as substitutes for loss of endogenous estrogens at menopause. To examine the roles of estrogen receptor α (ERα) and aryl hydrocarbon receptor (AhR) and their crosstalk in the actions of BEs, we studied gene regulation and proliferation responses to four widely used BEs, genistein, daidzein, and S-equol from soy, and liquiritigen from licorice root in breast cancer and liver cells. BEs and estradiol (E2), acting through ERα, stimulated proliferation, ERα chromatin binding and target-gene expression. BEs but not E2, acting through AhR, bound to xenobiotic response element-containing chromatin sites and enhanced AhR target-gene expression (CYP1A1, CYP1B1). While E2 and TCDD acted quite selectively through their respective receptors, BEs acted via both receptors, with their AhR activity moderated by negative crosstalk through ERα. Both ERα and AhR should be considered as mediators of the biology and pharmacology of BEs.
AB - Botanical estrogen (BE) dietary supplements are consumed by women as substitutes for loss of endogenous estrogens at menopause. To examine the roles of estrogen receptor α (ERα) and aryl hydrocarbon receptor (AhR) and their crosstalk in the actions of BEs, we studied gene regulation and proliferation responses to four widely used BEs, genistein, daidzein, and S-equol from soy, and liquiritigen from licorice root in breast cancer and liver cells. BEs and estradiol (E2), acting through ERα, stimulated proliferation, ERα chromatin binding and target-gene expression. BEs but not E2, acting through AhR, bound to xenobiotic response element-containing chromatin sites and enhanced AhR target-gene expression (CYP1A1, CYP1B1). While E2 and TCDD acted quite selectively through their respective receptors, BEs acted via both receptors, with their AhR activity moderated by negative crosstalk through ERα. Both ERα and AhR should be considered as mediators of the biology and pharmacology of BEs.
KW - Aryl hydrocarbon receptor
KW - Botanical estrogens
KW - Cell proliferation
KW - Estrogen receptor
KW - Gene regulation
KW - Xenobiotic metabolism
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U2 - 10.1016/j.mce.2016.08.025
DO - 10.1016/j.mce.2016.08.025
M3 - Article
C2 - 27543265
AN - SCOPUS:84983607497
SN - 0303-7207
VL - 437
SP - 190
EP - 200
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -