کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2196274 | 1550913 | 2012 | 9 صفحه PDF | دانلود رایگان |
The two estrogen receptor isoforms ERα and ERβ mediate biological effects of estrogens, but are also targets for endocrine disruptive chemicals (EDCs), compounds that interfere with hormonal signaling. 3-Methylcholanthrene (3-MC) and dioxin (TCDD) are EDCs and prototypical aryl hydrocarbon receptor (AhR) agonists, and can inhibit ER signaling. However, in contrast to TCDD, 3-MC gives rise to metabolites with estrogenic properties.We compared gene expression profiles in HepG2 cells after exposure to 3-MC, TCDD, and the synthetic estrogen diethylstilbestrol (DES). Interestingly, we observed little overlap between the genetic networks activated by 3-MC and TCDD, two compounds sometimes considered as interchangeable AhR ligands. Like DES, 3-MC induced a number of ER-regulated genes and lead to recruitment of ERα to the promoters of such genes. Interestingly, in contrast to DES, the estrogenic effects exerted by 3-MC were exclusively observed in ERα, but not in ERβ-expressing cells, suggesting ER isoform selectivity of 3-MC-derived metabolites.
► The two prototypical AhR agonists 3-MC and TCDD induce distinct sets of genes in HepG2 cells.
► 3-MC regulates 3× more genes than TCDD, probably by forming active metabolites.
► 3-MC metabolites activate ER target genes by recruiting ERα to their promoters.
► 3-MC acts only via ERα, not via ERβ.
► Follistatin is a novel direct ER-target gene and is induced by 3-MC.
Journal: Molecular and Cellular Endocrinology - Volume 362, Issues 1–2, 15 October 2012, Pages 39–47