Back to Search
Start Over
Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors
- Source :
- Toxicology and Applied Pharmacology, Toxicology and Applied Pharmacology, 2014, 280 (1), pp.60-69. ⟨10.1016/j.taap.2014.07.020⟩, Toxicol Appl Pharmacol, Toxicology and Applied Pharmacology, Elsevier, 2014, 280 (1), pp.60-69. ⟨10.1016/j.taap.2014.07.020⟩
- Publication Year :
- 2014
- Publisher :
- HAL CCSD, 2014.
-
Abstract
- International audience; : 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.
- Subjects :
- Molecular Sequence Data
Danio
Estrogen receptor
[SDV.CAN]Life Sciences [q-bio]/Cancer
Estrogen receptors
Pharmacology
Toxicology
reporter cell lines
Article
HeLa
[SDV.CAN] Life Sciences [q-bio]/Cancer
Genes, Reporter
medicine
Animals
Humans
Amino Acid Sequence
Receptor
Zebrafish
Binding Sites
biology
Dose-Response Relationship, Drug
selective estrogens
PHTPP
Estrogens
Environmental Exposure
biology.organism_classification
zebrafish
Cell biology
[SDV.TOX] Life Sciences [q-bio]/Toxicology
endocrine disruptors
Receptors, Estrogen
Cell culture
[SDV.TOX]Life Sciences [q-bio]/Toxicology
Female
Tamoxifen
medicine.drug
HeLa Cells
Subjects
Details
- Language :
- English
- ISSN :
- 0041008X and 10960333
- Database :
- OpenAIRE
- Journal :
- Toxicology and Applied Pharmacology, Toxicology and Applied Pharmacology, 2014, 280 (1), pp.60-69. ⟨10.1016/j.taap.2014.07.020⟩, Toxicol Appl Pharmacol, Toxicology and Applied Pharmacology, Elsevier, 2014, 280 (1), pp.60-69. ⟨10.1016/j.taap.2014.07.020⟩
- Accession number :
- edsair.doi.dedup.....4c44ccdb2b347b8a8c63f9e184eae98f