Reporter cell lines to evaluate the selectivity of chemicals for human and zebrafish estrogen and peroxysome proliferator activated ? receptors.

ABSTRACT: Zebrafish is increasingly used as an animal model to study the effects of environmental nuclear receptors (NRs) ligands. As most of these compounds have only been tested on human NRs, it is necessary to measure their effects on zebrafish NRs. Estrogen receptors (ER) ? and ? and peroxysome proliferator activated receptor (PPAR) ? are main targets of environmental disrupting compounds (EDCs). In humans there are two distinct nuclear ERs (hER? and hER?), whereas the zebrafish genome encodes three ERs, zfER?, zfER?1, and zfER?2. Only one isoform of PPAR? is expressed in both humans and zebrafish. In this review, we described reporter cell lines that we established to study the interaction of EDCs with human and zebrafish ERs and PPAR?. Using these cell lines, we observed that zfERs are thermo-sensitive while zfPPAR? is not. We also showed significant differences in the ability of environmental and synthetic ligands to modulate activation of zfERs and zfPPAR? in comparison to hERs and hPPAR?. Some environmental estrogens (bisphenol A, mycoestrogens) which are hER panagonists displayed greater potency for zfER? as compared to zfER?s. hER? selective agonists (8?VE2, DPN, phytoestrogens) also displayed zfER? selectivity. Among hER? selective synthetic agonists, 16?-LE2 was the most zfER? selective compound. Almost all zfPPAR? environmental ligands (halogenated bisphenol A derivatives, phthalates, perfluorinated compounds) displayed similar affinity for human and zebrafish PPAR? while pharmaceutical hPPAR? agonists like thiazolidones are not recognized by zfPPAR?. Altogether, our studies show that all hERs and hPPAR? ligands do not control in a similar manner the transcriptional activity of zfERs and zfPPAR? and point out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology.

SUBMITTER: Grimaldi M 

PROVIDER: S-EPMC4460427 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature