Dioxin induces an estrogen-like, estrogen receptor-dependent gene expression response in the murine uterus.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that elicits a broad range of toxicities in a tissue-, sex-, age-, and species-specific manner, including alterations in estrogen signaling. Many, if not all, of these effects involve changes in gene expression mediated via the activation of the aryl hydrocarbon receptor (AhR), a ligand activated transcription factor. Recent data indicate that TCDD may also elicit AhR-mediated estrogenic activity through interactions with the estrogen receptor (ER). In an effort to further characterize the estrogenic activity of TCDD, a comprehensive time-course analysis of uterine gene expression was conducted using ovariectomized C57BL/6 mice. Comparison of the temporal uterine transcriptional response to TCDD with that of ethynyl estradiol (EE) revealed a large proportion of the TCDD-mediated gene expression changes were also responsive to EE. Furthermore, pretreatment of mice with the pure ER antagonist ICI 182 780 (faslodex) inhibited gene expression responses to both EE and TCDD, providing additional evidence that these transcriptional responses involve the ER.
Boverhof
Darrell R
DR
Michigan State University, Department of Biochemistry and Molecular Biology, 501 Biochemistry Building, Wilson Road, East Lansing, MI 48824-1319, USA.
Kwekel
Joshua C
JC
Humes
Daryl G
DG
Burgoon
Lyle D
LD
Zacharewski
Timothy R
TR
D000818:Animals; D004147:Dioxins / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000502:physiology*
D004147:Dioxins; D004967:Estrogens; D000072317:Polychlorinated Dibenzodioxins; D011960:Receptors, Estrogen