Reciprocal inhibiting interactive mechanism between the estrogen receptor and aryl hydrocarbon receptor signaling pathways in goldfish (Carassius auratus) exposed to 17β-estradiol and benzo[a]pyrene

Comp Biochem Physiol C Toxicol Pharmacol. 2012 Jun;156(1):17-23. doi: 10.1016/j.cbpc.2012.03.001. Epub 2012 Mar 9.

Abstract

In the aquatic environment, both the estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) responses are established biomarkers for assessing exposure to pollutants. These receptor responses can also be affected by the presence of other classes of pollutants and may result in misinterpretation of existing pollution. In this study, we investigated the interaction between ER-vitellogenin (VTG) and AhR-cytochrome P450 1A (CYP1A) signaling pathways in goldfish (Carassius auratus) after 10 days exposure to pollutants. 17β-Estradiol (E(2)) and benzo[a]pyrene (BaP) were selected as the ER and AhR agonists, respectively. The messenger RNA (mRNA) expression of ER-VTG and AhR-CYP1A in liver was determined using quantitative real-time polymerase chain reaction (QRT-PCR). VTG, endogenous E(2) and 7-ethoxyresorufin-O-deethylase (EROD) were also studied. Exposure to E(2) and BaP alone significantly induced the gene expression of ERα-VTG and AhR2-CYP1A, respectively. Moreover, the obvious expression of related proteins was also observed. However, these inductions were significantly reduced after combined exposure to E(2) and lower concentrations of BaP (20 and 50 μg/L), indicative of a reciprocal inhibiting ER-AhR interaction. However, high concentrations (100 μg/L) of BaP did not affect the E(2)-induced gene expression. Changes in VTG protein were in accordance with the expression of VTG mRNA, and more VTG protein was observed in liver than in serum. The induced endogenous E(2) levels were suppressed by the presence of BaP. While the gene expression of CYP1A showed a concentration-dependent increase, EROD induction exhibited a bell-shaped concentration-response curve. Taken together, these results demonstrate a reciprocal inhibiting mode of ER-AhR interactions and may lead to a possible underestimation of actual exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzo(a)pyrene / toxicity*
  • Cytochrome P-450 CYP1A1 / blood
  • Cytochrome P-450 CYP1A1 / toxicity
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • Egg Proteins / genetics
  • Egg Proteins / metabolism
  • Estradiol / blood
  • Estradiol / toxicity*
  • Gene Expression / drug effects
  • Goldfish / genetics*
  • Goldfish / metabolism*
  • Liver / metabolism
  • Male
  • RNA, Messenger / genetics
  • Receptors, Aryl Hydrocarbon / agonists*
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Receptors, Estrogen / antagonists & inhibitors*
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • Signal Transduction / drug effects
  • Water Pollutants, Chemical / toxicity

Substances

  • Egg Proteins
  • RNA, Messenger
  • Receptors, Aryl Hydrocarbon
  • Receptors, Cell Surface
  • Receptors, Estrogen
  • Water Pollutants, Chemical
  • vitellogenin receptor
  • Benzo(a)pyrene
  • Estradiol
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A1