title: Effects of bisphenol A and triclocarban on brain-specific expression of aromatase in early zebrafish embryos.
abstract: Estrogen regulates numerous developmental and physiological processes. Most effects are mediated by estrogen receptors (ERs), which function as ligand-regulated transcription factors. Estrogen also regulates the activity of GPR30, a membrane-associated G protein-coupled receptor. Many different types of environmental contaminants can activate ERs; some can bind GPR30 as well. There is growing concern that exposure to some of these compounds, termed xenoestrogens, is interfering with the behavior and reproductive potential of numerous wildlife species, as well as affecting human health. Here, we investigated how two common, environmentally pervasive chemicals affect the in vivo expression of a known estrogen target gene in the brain of developing zebrafish embryos, aromatase AroB, which converts androgens to estrogens. We confirm that, like estrogen, the well-studied xenoestrogen bisphenol A (BPA, a plastics monomer), induces strong brain-specific overexpression of aromatase. Experiments using ER- and GPR30-selective modulators argue that this induction is largely through nuclear ERs. BPA induces dramatic overexpression of AroB RNA in the same subregions of the developing brain as estrogen. The antibacterial triclocarban (TCC) by itself stimulates AroB expression only slightly, but TCC strongly enhances the overexpression of AroB that is induced by exogenous estrogen. Thus, both BPA and TCC have the potential to elevate levels of aromatase and, thereby, levels of endogenous estrogens in the developing brain. In contrast to estrogen, BPA-induced AroB overexpression was suppressed by TCC. These results indicate that exposures to combinations of certain hormonally active pollutants can have outcomes that are not easily predicted from their individual effects.
authors: Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
authors: Eunah
authors: E
authors: Chung
authors: Maria C
authors: MC
authors: Genco
authors: Laura
authors: L
authors: Megrelis
authors: Joan V
authors: JV
authors: Ruderman
mesh_terms: D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D001559:Benzhydryl Compounds; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002224:Carbanilides / Q000633:toxicity*; D045744:Cell Line, Tumor; D004785:Environmental Pollutants / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D015151:Immunoblotting; D017403:In Situ Hybridization; D010636:Phenols / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D011959:Receptors, Estradiol / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism; D029961:Zebrafish Proteins; D000098826:Bisphenol A Compounds
chemical_list: D001141:Aromatase; D001559:Benzhydryl Compounds; D002224:Carbanilides; D004785:Environmental Pollutants; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011959:Receptors, Estradiol; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; D029961:Zebrafish Proteins; C549840:gper1 protein, zebrafish; C009540:triclocarban; C006780:bisphenol A; D000098826:Bisphenol A Compounds