TY - JOUR
T1 - Modulation of AhR-mediated CYP1A1 mRNA and EROD activities by 17β-estradiol and dexamethasone in TCDD-induced H411E cells
AU - Lai, K. P.
AU - Wong, M. H.
AU - Wong, Chris K.C.
N1 - Funding Information:
This work was supported by Group Research–Central Allocation of the Research Grants Council, University Grants Committee of Hong Kong.
PY - 2004/3
Y1 - 2004/3
N2 - 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.
AB - 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.
KW - 17β-estradiol
KW - CYP1A1 mRNA
KW - Dexamethasone
KW - EROD
KW - H411E cells
UR - http://www.scopus.com/inward/record.url?scp=1542686227&partnerID=8YFLogxK
U2 - 10.1093/toxsci/kfh045
DO - 10.1093/toxsci/kfh045
M3 - Journal article
C2 - 14691211
AN - SCOPUS:1542686227
SN - 1096-6080
VL - 78
SP - 41
EP - 49
JO - Toxicological Sciences
JF - Toxicological Sciences
IS - 1
ER -