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

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• 作者：Tian ; Yanan ; Ke ; Sui ; Thomas ; Thresia ; Meeker ; Robert J. ; Gallo ; Michael A.
• 关键词：gene regulation ; TCDD ; hnRNA ; mRNA ; estrogen receptor
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：1998
• 出版时间：October, 1998
• 年：1998
• 卷：67
• 期：1
• 页码：17-24
• 全文大小：433 K

文摘

TCDD, the most potent congener of the polychlorinated dioxins, has been shown to be an antiestrogen. The mechanisms of TCDD-induced antiestrogenicity are still under investigation. In this study, we investigated the effects of TCDD on the expression of the estrogen receptor (ER) gene. We studied the levels of un-spliced ER transcript (hnRNA) as well as the ER mRNA in ovary, uterus and liver of TCDD-treated mice with different genetic backgrounds. To quantitate the ER hnRNA levels, the intron and exon boundary of ER hnRNA was amplified by competitive RT-PCR. The ER mRNA from these mice was quantitated by competitive RT-PCR amplifying exons separated by an intron. ER hnRNA and ER mRNA levels were quantitated 4days after a single i.p. dose of TCDD (5μg/kg) in female C57BL/6J (B6) mice, which carry the responsive allele to TCDD. TCDD treatment significantly (p<0.05) suppressed the levels of ER hnRNA in the ovary (27.4 % ) and uterus (21.9 % ). The decreases in ER hnRNA were coordinated with significant (p<0.01) decreases in ER mRNA in ovary (57.7 % ) and uterus (37.6 % ). There was a significant decrease (20.3 % , p<0.05) in liver ER mRNA, however, the changes of ER hnRNA in liver were not significant. The coordinated decreases in ER hnRNA and mRNA in TCDD-treated mice suggest a suppression of transcription of the ER gene. We performed the same study on DBA/2J (D2) mice, which possess the “non-responsive” allele of the aryl hydrocarbon receptor (AhR). These mice demonstrated no significant decrease in either the ER mRNA or hnRNA after TCDD treatment. Overall, these results suggest that TCDD suppresses the gene expression of the ER receptor by decreasing its transcription, and the AhR plays an important role in mediating this response. Publisher: Elsevier Science Language of Publication: English Item Identifier: S0960-0760(98)00067-3 Publication Type: Article ISSN: 0960-0760 Cited by:

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Footnotes:

1. Part of the work communicated in this paper was presented in the 82nd (Toronto, Canada) Annual Meetings of the Endocrine Society. All cDNA clones used in the present experiments are available from the laboratory of Professor Hutz.