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.

• Authors: Ping Gong, Zeynep Madak-Erdogan, Jodi A Flaws, David J Shapiro, John A Katzenellenbogen, Benita S Katzenellenbogen
• Journal: Molecular and cellular endocrinology (Mol Cell Endocrinol) Vol. 437 Pg. 190-200 (12 05 2016) ISSN: 1872-8057 [Electronic] Ireland
• PMID: 27543265 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Chromatin
• ESR1 protein, human
• Estrogen Receptor alpha
• Estrogens
• Polychlorinated Dibenzodioxins
• RNA, Small Interfering
• Receptors, Aryl Hydrocarbon
• Receptors, Progesterone
• Estradiol
• CYP1A1 protein, human
• CYP1B1 protein, human
• Cytochrome P-450 CYP1A1
• Cytochrome P-450 CYP1B1

Topics

• Binding Sites
• Breast Neoplasms (genetics, pathology)
• Cell Proliferation (drug effects)
• Chromatin (metabolism)
• Cytochrome P-450 CYP1A1 (genetics, metabolism)
• Cytochrome P-450 CYP1B1 (genetics, metabolism)
• Dose-Response Relationship, Drug
• Estradiol (pharmacology)
• Estrogen Receptor alpha (genetics, metabolism)
• Estrogens (pharmacology)
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Hep G2 Cells
• Humans
• MCF-7 Cells
• Models, Biological
• Polychlorinated Dibenzodioxins (pharmacology)
• RNA, Small Interfering (metabolism)
• Receptors, Aryl Hydrocarbon (genetics, metabolism)
• Receptors, Progesterone (metabolism)