Send to

Choose Destination
Toxicol Sci. 2004 Mar;78(1):41-9. Epub 2003 Dec 22.

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

Author information

Institute for Natural Resources and Environmental Management, and Department of Biology, Hong Kong Baptist University, Hong Kong, PR China.


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, 17beta-estradiol (E(2)), diethylstilbestrol (DES), testosterone (T), 5alpha-dihydrotestosterone (DHT), dexamethasone (DEX), and T(3), 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 E(2)/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. E(2)-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, E(2)-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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center