Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17β-estradiol and dexamethasone in TCDD-induced H411E cells

K. P. Lai, Ming Hung WONG, Chris K C WONG*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

44 Citations (Scopus)

Abstract

TCDD elicits a variety of species- and organ-specific pathological consequences. The differential toxicities are thought to relate to the de novo modulation of TCDD action by endogenous hormones. Previous studies from this laboratory demonstrated a dose-and time-dependent induction of CYP1A1 expression and 7-ethoxyresorufin-O-deethylase (EROD) activities in H4IIE cells by picomolar levels of TCDD treatment. In this study, we examined the hormonal modulation of TCDD-elicited AhR-mediated biochemical responses. Lipid-soluble hormones, 17β-estradiol (E2), diethylstilbestrol (DES), testosterone (T), 5α-dihydrotestosterone (DHT), dexamethasone (DEX), and T3 were studied for their possible interactions with the TCDD-mediated effects. Our results showed that CYP1A1 expression and EROD activities induced by TCDD were potentiated or suppressed, respectively, by DEX or E2/DES treatment. Other tested hormones, however, had no significant effect. Using a receptor antagonist (RU486), DEX-mediated potentiation of TCDD-elicited EROD activity was completely abolished. E2-mediated suppression, however, was not affected by cotreatment with the estrogen receptor antagonists, 4-hydroxytamoxifen or ICI 182780. Taking a step further to dissect the possible mechanisms involved, with the aid of cycloheximide (CHX), DEX-mediated potentiation was found to depend on the posttranscriptional process. The DEX pretreatment study indicated that the potentiation was a time-dependent process. In contrast, E2-mediated suppression did not rely on the synthesis of protein factors. Presumably it might hinder the formation of the activated TCDD/AhR complex and so the subsequent binding on DRE.

Original languageEnglish
Pages (from-to)41-49
Number of pages9
JournalToxicological Sciences
Volume78
Issue number1
DOIs
Publication statusPublished - Mar 2004

Scopus Subject Areas

  • Toxicology

User-Defined Keywords

  • 17β-estradiol
  • CYP1A1 mRNA
  • Dexamethasone
  • EROD
  • H411E cells

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