title: Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17beta-estradiol and dexamethasone in TCDD-induced H411E cells.
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, 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.
authors.affiliation: Institute for Natural Resources and Environmental Management, and Department of Biology, Hong Kong Baptist University, Hong Kong, PR China.
authors.forename: K P
authors.initials: KP
authors.lastname: Lai
authors.forename: M H
authors.initials: MH
authors.lastname: Wong
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003513:Cycloheximide / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D017931:DNA Primers; D003907:Dexamethasone / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000633:toxicity*; D004958:Estradiol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000201:enzymology / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011499:Protein Processing, Post-Translational / Q000502:physiology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000199:Actins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D017931:DNA Primers; D004785:Environmental Pollutants; D006728:Hormones; D000072317:Polychlorinated Dibenzodioxins; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D004958:Estradiol; D003907:Dexamethasone; D003513:Cycloheximide; D019363:Cytochrome P-450 CYP1A1