PMID- 20739074
OWN - NLM
STAT- MEDLINE
DCOM- 20101216
LR  - 20131121
IS  - 1879-1514 (Electronic)
IS  - 0166-445X (Linking)
VI  - 100
IP  - 3
DP  - 2010 Nov 1
TI  - One-way inhibiting cross-talk between arylhydrocarbon receptor (AhR) and estrogen 
      receptor (ER) signaling in primary cultures of rainbow trout hepatocytes.
PG  - 263-70
LID - 10.1016/j.aquatox.2010.07.024 [doi]
AB  - The aryl hydrocarbon receptor (AhR) and the estrogen receptor (ER) are 
      ligand-activated transcription factors, both of which can be activated by 
      environmental pollutants. The AhR regulates cytochrome P450 1A (CYP1A) expression 
      and can be induced by aromatic hydrocarbons. The ER regulates vitellogenin (VTG) 
      expression and can be induced by estrogenic substances. Both receptor responses 
      are established biomarkers used to assess the effects of pollutants in the 
      aquatic environment. The receptors can also be affected in situations of mixed 
      exposure. Cross-talk between these receptor pathways has been suggested, although 
      there are conflicting data in the literature. We investigated cross-talk between 
      ER-VTG and AhR-CYP1A signaling pathways in primary cultures of rainbow trout 
      hepatocytes, using quantitative PCR (qPCR) for mRNA analyses and studies of CYP1A 
      catalytic function and protein expression. The model agonists beta-naphthoflavone 
      (BNF) and 17alpha-ethinylestradiol (EE(2)) were used for AhR and ER activation, 
      respectively. Combined exposure to BNF and EE(2) reduced the EE(2)-mediated 
      induction of VTG mRNA levels by about 40%, but had no effect on the BNF-mediated 
      CYP1A mRNA levels, indicative of a one-way inhibiting AhR-ER cross-talk. However, 
      basal levels of CYP1A mRNA were reduced 40% upon exposure to EE(2) alone, 
      implying different cross-talk mechanism between basal and induced CYP1A mRNA 
      levels. The mammalian ER antagonist fulvestrant (ICI) is commonly described as an 
      absolute ER antagonist. However, ICI failed to reverse the ER activation caused 
      by EE(2) in the present study. The CYP1A-mediated ethoxyresorufin-O-deethylase 
      (EROD) activity was reduced by 80% in cells co-treated with BNF and EE(2), 
      compared to cells exposed to BNF alone. In vitro inhibiting studies suggests that 
      this reduction was a result of inhibition of the CYP1A catalyst by EE(2) since 
      EE(2) acted as a potent inhibitor (IC(50): 4.6muM) of the EROD activity. In 
      addition, ICI also acted as a potent inhibitor of the EROD enzyme (IC(50): 
      0.6muM). Taken together, our data supports a one-way inhibiting AhR-ER cross-talk 
      in rainbow trout hepatocytes exposed to a mixture of BNF and EE(2).
CI  - Copyright (c) 2010 Elsevier B.V. All rights reserved.
FAU - Grans, Johanna
AU  - Grans J
AD  - University of Gothenburg, Department of Zoology, SE-405 30 Goteborg, Sweden.
FAU - Wassmur, Britt
AU  - Wassmur B
FAU - Celander, Malin C
AU  - Celander MC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100727
PL  - Netherlands
TA  - Aquat Toxicol
JT  - Aquatic toxicology (Amsterdam, Netherlands)
JID - 8500246
RN  - 0 (Receptors, Aryl Hydrocarbon)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Vitellogenins)
RN  - 0 (Water Pollutants, Chemical)
RN  - 423D2T571U (Ethinyl Estradiol)
RN  - 6051-87-2 (beta-Naphthoflavone)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Ethinyl Estradiol/toxicity
MH  - Hepatocytes/drug effects/*metabolism
MH  - Oncorhynchus mykiss/*metabolism
MH  - *Receptor Cross-Talk
MH  - Receptors, Aryl Hydrocarbon/drug effects/*metabolism
MH  - Receptors, Estrogen/drug effects/*metabolism
MH  - Signal Transduction/drug effects
MH  - Vitellogenins/metabolism
MH  - Water Pollutants, Chemical/toxicity
MH  - beta-Naphthoflavone/toxicity
EDAT- 2010/08/27 06:00
MHDA- 2010/12/17 06:00
CRDT- 2010/08/27 06:00
PHST- 2010/04/08 00:00 [received]
PHST- 2010/07/15 00:00 [revised]
PHST- 2010/07/21 00:00 [accepted]
PHST- 2010/08/27 06:00 [entrez]
PHST- 2010/08/27 06:00 [pubmed]
PHST- 2010/12/17 06:00 [medline]
AID - S0166-445X(10)00272-9 [pii]
AID - 10.1016/j.aquatox.2010.07.024 [doi]
PST - ppublish
SO  - Aquat Toxicol. 2010 Nov 1;100(3):263-70. doi: 10.1016/j.aquatox.2010.07.024. Epub 
      2010 Jul 27.