Transcriptional suppression of estrogen receptor gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Yan, Tian; Ke, Sui; Thomas, Thresia; Meeker, Robert J.; Gallo, Michael A.

doi:10.1016/s0960-0760(98)00067-3

Cited by 76 publications

(43 citation statements)

References 35 publications

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“…Our results add to the growing number of mechanisms whereby the AhR modulates estrogenic activity. Antiestrogenic effects of AhR ligands, in particular, have been extensively studied, and several mechanisms underlying such effects have been reported (for review, see Safe and Wormke, 2003), including the following; 1) AhR-mediated induction of enzymes (e.g., CYP1B1) that metabolize estrogens and thereby reduce tissue estrogen concentrations (Takemoto et al, 2004); 2) AhR-mediated induction of a transcription inhibitory factor (Rogers and Denison, 2002); 3) an inhibitory action mediated by the nonproductive binding of liganded AhR to an ER target gene, which prevents ER from binding (Krishnan et al, 1995); 4) AhR-mediated reduction of cellular ER levels by either suppression of ER transcription (Tian et al, 1998) or acceleration of ER degradation ; and 5) AhR-mediated transcriptional activation of its target genes, resulting in competition for recruitment of the limited pool of coactivators that are shared by the AhR and ER. In this regard, ARNT is said to function as a coactivator for ER, but with selectivity for ER␤.…”

Section: Downloaded Frommentioning

confidence: 99%

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Fu¹,

Fang²,

Paulsen³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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Estrogen sulfotransferase (SULT1E1) catalyzes the sulfonation of estrogens, which limits estrogen mitogenicity. We recently reported that SULT1E1 expression is low in preconfluent MCF10A human breast epithelial cells but increases when the cells become confluent. Pulse-chase labeling experiments with 5-bromouridine demonstrated that the confluence-mediated increase in SULT1E1 expression was due to increased mRNA synthesis. Because aryl hydrocarbon receptor (AhR) activation has been shown to suppress SULT1E1 expression and loss of cell-cell contact has been shown to activate the AhR in other cell types, we tested whether the confluence-associated changes in SULT1E1 expression were mediated by the AhR. Relative to confluent MCF10A cells, preconfluent cells had higher levels of CYP1A1 mRNA and greater activation of an AhR-responsive luciferase reporter, demonstrating that the AhR was active in the preconfluent cells. AhR and aryl hydrocarbon receptor nuclear translocator mRNA and protein levels were also higher in preconfluent than in confluent cultures. Treatment of preconfluent cells with the AhR antagonist, 3Ј-methoxy-4Ј-nitroflavone (MNF), or AhR knockdown significantly increased SULT1E1 expression. MCF10A cells stably transfected with a luciferase reporter containing ϳ7 kilobases of the SULT1E1 5Ј-flanking region showed both MNF-and confluence-inducible luciferase expression. Preconfluent cells transiently transfected with the reporter showed both MNF treatment-and AhR knockdown-mediated luciferase induction, but mutation of a computationally predicted dioxin response element (DRE) at nucleotide (nt) Ϫ3476 did not attenuate these effects. These results demonstrate that SULT1E1 expression in MCF10A cells is transcriptionally regulated by confluence through a suppressive action of the AhR, which is not mediated through a DRE at nt Ϫ3476.

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Section: Downloaded Frommentioning

confidence: 99%

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Fu¹,

Fang²,

Paulsen³

et al. 2011

The Journal of Pharmacology and Experimental Therapeutics

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“…Caruso et al (1999) investigated the 90kDa-heat shock protein (HSP90) as a mediator of Some authors suggest that the TCDD receptor may be related to the estrogen receptor and that the antiestrogenic action of TCDD is probably independent of the Ah locus (Gallo et al, 1986). Tian et al (1998) showed that TCDD suppresses the gene expression of the ER receptor by decreasing its transcription and that the AhR plays an important role in mediating this response. Kharat & Saatcioglu (1996) hypothesized that activated AhR competes with ER for some limiting transcription factor(s).…”

Section: Dose Response Curvementioning

confidence: 99%

Dioxin exposure and porcine reproductive hormonal activity

Gregoraszczuk

2002

Cad. Saúde Pública

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“…A number of possible mechanisms, nevertheless, have been suggested for the anti-estrogenic actions of TCDD, which include stimulation of estrogen metabolism [14,15], a possible direct antiestrogenic action [13,16,17], and also possible alterations of the binding interaction between the estrogen receptor and its response element [18,19]. Since TCDD is an extremely potent agonist for the aryl hydrocarbon receptor (AhR), which mediates the induction of a number of drug-metabolizing enzymes in liver as well as in extrahepatic tissues [20], it has been widely considered that chronic TCDD administration may alter the multiple pathways of endogenous estrogen metabolism in certain ways that may contribute to an altered hormonal activity and also tumor incidence in various estrogen target organs.…”

Section: Introductionmentioning

confidence: 99%

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin administration and high-fat diet on the body weight and hepatic estrogen metabolism in female C3H/HeN mice

Zhu

Gallo

Burger

et al. 2008

Toxicology and Applied Pharmacology

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We studied the effect of administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) by i.p. injection once every two weeks in combination with a high-fat (HF) diet for 8 or 16 weeks on the body and organ weight changes as well as on the hepatic enzyme activity for estrogen metabolism in C3H/HeN female mice. Administration of TCDD at 100 μg/kg b.w. once every two weeks for 8 weeks increased the body weight by 46% in the HF diet-fed animals, but not in the regular diet-fed animals. This is the first observation suggesting that TCDD, a potent Ah receptor agonist, may have an obesity-inducing effect in animals fed a HF diet. While TCDD increased liver weight and decreased thymus weight in animals, these effects were enhanced by feeding animals a HF diet. Metabolism studies showed that TCDD administration for 8 or 16 weeks increased the liver microsomal activity for the 2-and 4-hydroxylation of 17β-estradiol in animals fed a control diet, but surprisingly not in animals fed a HF diet. Treatment with TCDD dose-dependently increased the hepatic activity for the O-methylation of catechol estrogens in both control and HF diet-fed animals, and it also decreased the levels of liver microsomal sulfatase activity for hydrolysis of estrone-3-sulfate. TCDD did not significantly affect the hepatic enzyme activity for the glucuronidation or esterification of endogenous estrogens. It is suggested that enhanced metabolic inactivation of 1 This study was supported, in part, by a grant from the American Cancer Society (RSG-02-143-01-CNE to BTZ) and also by grants from the NIH (CA92391, CA97109 and ES05022). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. endogenous estrogens by hepatic estrogen-metabolizing enzymes in TCDD-treated, control diet-fed animals contributes importantly to the reduced incidence of estrogen-associated tumors in animals treated with TCDD. NIH Public Access

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Transcriptional suppression of estrogen receptor gene expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)

Cited by 76 publications

References 35 publications

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Regulation of Estrogen Sulfotransferase Expression by Confluence of MCF10A Breast Epithelial Cells: Role of the Aryl Hydrocarbon Receptor

Dioxin exposure and porcine reproductive hormonal activity

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin administration and high-fat diet on the body weight and hepatic estrogen metabolism in female C3H/HeN mice

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