PUBLICATION

Mixture Concentration-Response Modeling Reveals Antagonistic Effects of Estradiol and Genistein in Combination on Brain Aromatase Gene (cyp19a1b) in Zebrafish

Authors
Hinfray, N., Tebby, C., Piccini, B., Bourgine, G., Aït-Aïssa, S., Porcher, J.M., Pakdel, F., Brion, F.
ID
ZDB-PUB-180405-1
Date
2018
Source
International Journal of Molecular Sciences   19(4): (Journal)
Registered Authors
Keywords
U251-MG, aromatase B, estradiol, genistein, mixture, transgenic zebrafish
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Aromatase/genetics
  • Aromatase/metabolism*
  • Brain/drug effects
  • Brain/metabolism*
  • Estradiol/pharmacology*
  • Genistein/pharmacology*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed
29614754 Full text @ Int. J. Mol. Sci.
Abstract
Comprehension of compound interactions in mixtures is of increasing interest to scientists, especially from a perspective of mixture risk assessment. However, most of conducted studies have been dedicated to the effects on gonads, while only few of them were. interested in the effects on the central nervous system which is a known target for estrogenic compounds. In the present study, the effects of estradiol (E2), a natural estrogen, and genistein (GEN), a phyto-estrogen, on the brain ER-regulated cyp19a1b gene in radial glial cells were investigated alone and in mixtures. For that, zebrafish-specific in vitro and in vivo bioassays were used. In U251-MG transactivation assays, E2 and GEN produced antagonistic effects at low mixture concentrations. In the cyp19a1b-GFP transgenic zebrafish, this antagonism was observed at all ratios and all concentrations of mixtures, confirming the in vitro effects. In the present study, we confirm (i) that our in vitro and in vivo biological models are valuable complementary tools to assess the estrogenic potency of chemicals both alone and in mixtures; (ii) the usefulness of the ray design approach combined with the concentration-addition modeling to highlight interactions between mixture components.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping