کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5846190 1128461 2014 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors
چکیده انگلیسی


- Zebrafish is increasingly used to study the effects of estrogens.
- We assessed the activity of pharmaceutical and environmental estrogens on zfERs.
- Environmental estrogens displayed greater potency for zfERα compared to zfERβs.
- hERβ selective agonists displayed greater potency for zfERα compared to zfERβs.
- The hERα selective agonist 16αL-E2 is the most zfERα selective compound.

Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28 °C as compared to 37 °C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 280, Issue 1, 1 October 2014, Pages 60-69
نویسندگان
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