PMID- 15119955
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240314
IS  - 1476-5926 (Print)
IS  - 1476-5926 (Electronic)
IS  - 1476-5926 (Linking)
VI  - 3
IP  - 1
DP  - 2004 May 2
TI  - The aryl hydrocarbon receptor-mediated disruption of vitellogenin synthesis in 
      the fish liver: Cross-talk between AHR- and ERalpha-signalling pathways.
PG  - 2
AB  - BACKGROUND: In the fish liver, the synthesis of egg yolk protein precursor 
      vitellogenin (VTG) is under control of the estrogen receptor alpha (ERalpha). 
      Environmental contaminants such as 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) 
      are suspected to have antiestrogenic effects. The aryl hydrocarbon receptor (AHR) 
      is the initial cellular target for TCDD and related compounds. The AHR is a 
      ligand-activated transcription factor that stimulates the expression of the genes 
      encoding xenobiotic metabolizing enzymes, such as cytochrome P450 1A (CYP1A). In 
      this study, the effects of activation of AHR on the hepatic expression of VTG and 
      ERalpha genes, in primary cultured salmon hepatocytes, have been investigated. 
      RESULTS: The expression of the genes encoding VTG and ERalpha were strongly 
      induced by 17beta-estradiol (E2). However, the expression of VTG was disrupted by 
      exposure of the cells to TCDD while CYP1A expression was enhanced. The effect of 
      TCDD on VTG and CYP1A expression was annulled by the AHR-inhibitor 
      alpha-naphthoflavone. Furthermore, exposure of the cells to TCDD abolished 
      E2-induced accumulation of ERalpha mRNA. The AHR-mediated inhibitory effects on 
      the expression of the VTG and ERalpha genes may occur at transcriptional and/or 
      post-transcriptional levels. Nuclear run-off experiments revealed that 
      simultaneous exposure of the cells to E2 and TCDD strongly inhibited the 
      initiation of transcription of the VTG and ERalpha genes. In addition, inhibition 
      of RNA synthesis by actinomycin D treatment showed that post-transcriptional 
      levels of VTG and ERalpha mRNAs were not significantly altered upon treatment of 
      the cells with TCDD. These results suggested that activation of AHR may inhibit 
      the transactivation capacity of the ERalpha. Further, electrophoretic mobility 
      shift assays using nuclear extracts prepared from cells treated for one or two 
      hours with E2, alone or in mixture with TCDD, showed a strong reduction in the 
      DNA binding activities upon TCDD treatment. These results also suggested that 
      activation of the AHR signalling pathway caused a marked decrease in the number 
      of the nuclear ERalpha or that activated AHR blocked the ability of ERalpha to 
      bind to its target DNA sequence. Finally, our results from Northern 
      hybridizations indicated that E2 treatment of the cells did not cause any 
      significant effect on the TCDD-induced levels of CYP1A mRNA. CONCLUSION: In fish 
      hepatocytes E2 induces ERalpha and VTG gene expression. The presence of dioxin 
      (TCDD) abolishes this induction, probably through the action of AHR in complex 
      with AHR nuclear translocator, and possibly by direct interference with the 
      auto-regulatory transcriptional loop of ERalpha. Furthermore, E2 does not 
      interfere with TCDD induced CYP1A gene expression, suggesting that cross-talk 
      between the ERalpha- and AHR-signalling pathways is unidirectional.
FAU - Bemanian, Vahid
AU  - Bemanian V
AD  - Department of Molecular Biology, University of Bergen, POBox 7800, N-5020 Bergen, 
      Norway. Rune.Male@mbi.uib.no
FAU - Male, Rune
AU  - Male R
FAU - Goksoyr, Anders
AU  - Goksoyr A
LA  - eng
PT  - Journal Article
DEP - 20040502
PL  - England
TA  - Comp Hepatol
JT  - Comparative hepatology
JID - 101147643
PMC - PMC419714
EDAT- 2004/05/04 05:00
MHDA- 2004/05/04 05:01
PMCR- 2004/05/02
CRDT- 2004/05/04 05:00
PHST- 2003/09/05 00:00 [received]
PHST- 2004/05/02 00:00 [accepted]
PHST- 2004/05/04 05:00 [pubmed]
PHST- 2004/05/04 05:01 [medline]
PHST- 2004/05/04 05:00 [entrez]
PHST- 2004/05/02 00:00 [pmc-release]
AID - 1476-5926-3-2 [pii]
AID - 10.1186/1476-5926-3-2 [doi]
PST - epublish
SO  - Comp Hepatol. 2004 May 2;3(1):2. doi: 10.1186/1476-5926-3-2.