PUBLICATION
A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids Using In Vitro Reporter Gene Assays
- Authors
- Creusot, N., Garoche, C., Grimaldi, M., Boulahtouf, A., Chiavarina, B., Bourguet, W., Balaguer, P.
- ID
- ZDB-PUB-210605-4
- Date
- 2021
- Source
- Frontiers in endocrinology 12: 665521 (Journal)
- Registered Authors
- Keywords
- human PXR, pesticides, reporter cell lines, steroids, zebrafish PXR
- MeSH Terms
-
- Animals
- Biological Assay/methods*
- Gene Expression Regulation/drug effects*
- Genes, Reporter*
- Humans
- In Vitro Techniques
- Pesticides/pharmacology*
- Pregnane X Receptor/genetics
- Pregnane X Receptor/metabolism*
- Steroids/pharmacology*
- Zebrafish
- PubMed
- 34084152 Full text @ Front Endocrinol (Lausanne)
Citation
Creusot, N., Garoche, C., Grimaldi, M., Boulahtouf, A., Chiavarina, B., Bourguet, W., Balaguer, P. (2021) A Comparative Study of Human and Zebrafish Pregnane X Receptor Activities of Pesticides and Steroids Using In Vitro Reporter Gene Assays. Frontiers in endocrinology. 12:665521.
Abstract
The nuclear receptor pregnane X receptor (PXR) is a ligand-dependent transcription factor that regulates genes involved in xenobiotic metabolism in mammals. Many studies suggest that PXR may play a similar role in fish. The interaction of human PXR (hPXR) with a variety of structurally diverse endogenous and exogenous chemicals is well described. In contrast, little is known about the zebrafish PXR (zfPXR). In order to compare the effects of these chemicals on the PXR of these two species, we established reporter cell lines expressing either hPXR or zfPXR. Using these cellular models, we tested the hPXR and zfPXR activity of various steroids and pesticides. We provide evidence that steroids were generally stronger activators of zfPXR while pesticides were more potent on hPXR. In addition, some chemicals (econazole nitrate, mifepristone, cypermethrin) showed an antagonist effect on zfPXR, whereas no antagonist chemical has been identified for hPXR. These results confirm significant differences in the ability of chemicals to modulate zfPXR in comparison to hPXR and point out that zfPXR assays should be used instead of hPXR assays for evaluating the potential risks of chemicals on aquatic species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping