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

• Published in: The Journal of steroid biochemistry and molecular biology 1998-10, Vol.67 (1), p.17-24
• Main Authors: Tian, Yanan, Ke, Sui, Thomas, Thresia, Meeker, Robert J, Gallo, Michael A
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Biological and medical sciences; Chemical and industrial products toxicology. Toxic occupational diseases; estrogen receptor; Exons; Female; Gene Expression Regulation - drug effects; gene regulation; hnRNA; Introns; Liver - metabolism; Medical sciences; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Molecular Sequence Data; mRNA; Ovary - metabolism; Polychlorinated Dibenzodioxins - pharmacology; Polymerase Chain Reaction; Receptors, Estrogen - genetics; Regression Analysis; RNA, Heterogeneous Nuclear - genetics; RNA, Messenger - genetics; Species Specificity; TCDD; Toxicology; Transcription, Genetic - drug effects; Uterus - metabolism; Various organic compounds
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(98)00067-3

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 4 days after a single i.p. dose of TCDD (5 μg/kg) in female C57BL/6J (B6) mice, which carry the responsive allele to TCDD. TCDD treatment significantly ( p