| Added by | mollevi |
|---|---|
| Last modified by | Cavailles |
| Group name | EquipeVC |
| Item Type | Journal Article |
| Title | Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors |
| Creator | Pinto et al. |
| Author | C. Pinto |
| Author | M. Grimaldi |
| Author | A. Boulahtouf |
| Author | F. Pakdel |
| Author | F. Brion |
| Author | S. Ait-Aissa |
| Author | V. Cavailles |
| Author | W. Bourguet |
| Author | J. A. Gustafsson |
| Author | M. Bondesson |
| Author | P. Balaguer |
| Abstract | 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 (hERalpha and hERbeta), whereas the zebrafish genome encodes three ERs, zfERalpha and two zfERbetas (zfERbeta1 and zfERbeta2). 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 degrees C as compared to 37 degrees 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 hERbeta selective agonists displayed greater potency for zfERalpha as compared to zfERbetas. Among hERalpha selective synthetic agonists, PPT did not activate zfERalpha while 16alpha-LE2 was the most zfERalpha 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. |
| Publication | Toxicol Appl Pharmacol |
| Volume | 280 |
| Pages | 60-9 |
| Date | Oct 1 2014 |
| Journal Abbr | Toxicology and applied pharmacology |
| ISSN | 1096-0333 (Electronic) 0041-008X (Linking) |
| Tags | *Environmental Exposure/adverse effects, Amino Acid Sequence, Animals, Binding Sites/physiology, Dose-Response Relationship, Drug, Estrogens/chemistry/*metabolism/pharmacology, Female, Genes, Reporter/physiology, HeLa Cells, Humans, Molecular Sequence Data, original, own, Receptors, Estrogen/chemistry/genetics/*metabolism, Zebrafish |
| Date Added | 2018/11/14 - 12:10:52 |
| Date Modified | 2019/05/17 - 11:58:13 |
| Notes and Attachments | (Note) (Note) 25106122 (Attachment) |
Institut de Recherche en Cancérologie de
