ZFIN ID: ZDB-PUB-070210-14
Expression of Zebra Fish Aromatase cyp19a and cyp19b Genes in Response to the Ligands of Estrogen Receptor and Aryl Hydrocarbon Receptor
Cheshenko, K., Brion, F., Le Page, Y., Hinfray, N., Pakdel, F., Kah, O., Segner, H., and Eggen, R.I.
Date: 2007
Source: Toxicological sciences : an official journal of the Society of Toxicology   96(2): 255-267 (Journal)
Registered Authors: Kah, Olivier
Keywords: endocrine disruption, aromatase CYP19, zebra fishestrogen receptor, aryl hydrocarbon receptor, gene expression/regulation
MeSH Terms:
  • Animals
  • Aromatase/genetics*
  • Aromatase/metabolism
  • Aryl Hydrocarbon Receptor Nuclear Translocator/pharmacology
  • Benzo(a)pyrene/pharmacology
  • Benzoflavones/pharmacology
  • Cell Line
  • Estradiol/analogs & derivatives
  • Estradiol/pharmacology
  • Gene Expression Regulation, Enzymologic/drug effects*
  • Humans
  • Immunohistochemistry
  • Larva/drug effects
  • Larva/metabolism
  • Ligands
  • Luciferases/genetics
  • Luciferases/metabolism
  • Neuroglia/cytology
  • Neuroglia/drug effects
  • Neuroglia/metabolism
  • Promoter Regions, Genetic
  • RNA, Messenger/genetics
  • RNA, Messenger/metabolism
  • Receptors, Aryl Hydrocarbon/agonists*
  • Receptors, Aryl Hydrocarbon/antagonists & inhibitors
  • Receptors, Estrogen/agonists*
  • Receptors, Estrogen/antagonists & inhibitors
  • Transcription Factors/pharmacology
  • Zebrafish/genetics*
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
PubMed: 17234648 Full text @ Toxicol. Sci.
Many endocrine disrupting chemicals act via estrogen receptor (ER) or aryl hydrocarbon receptor (AhR). To investigate the interference between ER and AhR, we studied the effects of 17beta-estradiol (E2) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the expression of zebrafish cyp19a (zfcyp19a) and cyp19b (zfcyp19b) genes, encoding aromatase P450, an important steroidogenic enzyme. In vivo (mRNA quantification in exposed zebrafish larvae) and in vitro (activity of zfcyp19-luciferase reporter genes in cell cultures in response to chemicals and zebrafish transcription factors) assays were used. None of the treatments affected zfcyp19a, excluding the slight upregulation by E2 observed in vitro. Strong upregulation of zfcyp19b by E2 in both assays was downregulated by TCDD. This effect could be rescued by the addition of an AhR antagonist. Anti-estrogenic effect of TCDD on the zfcyp19b expression in the brain was also observed on the protein level, assessed by immunohistochemistry. TCDD alone did not affect zfcyp19b expression in vivo or promoter activity in the presence of zebrafish AhR2 and AhR nuclear translocator 2b (ARNT2b) in vitro. However, in the presence of zebrafish ERalpha, AhR2 and ARNT2b, TCDD led to a slight upregulation of promoter activity, which was eliminated by either an ER or AhR antagonist. Studies with mutated reporter gene constructs indicated that both mechanisms of TCDD action in vitro were independent of dioxin responsive elements (DREs) predicted in the promoter. This study shows the usefulness of in vivo zebrafish larvae and in vitro zfcyp19b reporter gene assays for evaluation of estrogenic chemical actions, provides data on the functionality of DREs predicted in zfcyp19 promoters and shows the effects of crosstalk between ER and AhR on zfcyp19b expression. The anti-estrogenic effect of TCDD demonstrated raises further concerns about the neuroendocrine effects of AhR ligands.