Abstract

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.

Original languageEnglish (US)
Pages (from-to)190-200
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume437
DOIs
StatePublished - Dec 5 2016

Fingerprint

Aryl Hydrocarbon Receptors
Estrogen Receptors
Estrogens
Gene expression
Crosstalk
Chromatin
Dietary supplements
Equol
Glycyrrhiza
Gene Expression
Cytochrome P-450 CYP1A1
Genistein
Response Elements
Xenobiotics
Liver Neoplasms
Menopause
Dietary Supplements
Liver
Estradiol
Pharmacology

Keywords

  • Aryl hydrocarbon receptor
  • Botanical estrogens
  • Cell proliferation
  • Estrogen receptor
  • Gene regulation
  • Xenobiotic metabolism

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Cite this

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title = "Estrogen receptor-α and aryl hydrocarbon receptor involvement in the actions of botanical estrogens in target cells",
abstract = "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.",
keywords = "Aryl hydrocarbon receptor, Botanical estrogens, Cell proliferation, Estrogen receptor, Gene regulation, Xenobiotic metabolism",
author = "Ping Gong and Zeynep Madak-Erdogan and Flaws, {Jodi A} and Shapiro, {David J} and Katzenellenbogen, {John A.} and Katzenellenbogen, {Benita S}",
year = "2016",
month = "12",
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doi = "10.1016/j.mce.2016.08.025",
language = "English (US)",
volume = "437",
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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

PY - 2016/12/5

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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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