2008/02/27 by Yukie Yanagiba, Yuki Ito, Osamu Yamanoshita +8 · 2 citations
Environmental Science · Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Toxic Organic Pollutants Impact #Effects and risks of endocrine disrupting chemicals #Carcinogens and Genotoxicity Assessment #Aryl hydrocarbon receptor #Internal medicine #Endocrinology #Chemistry #Cytochrome P450 #Thyroid #CYP2E1 #Endocrine system #Hormone #Biology #Metabolism #Biochemistry #Gene #Transcription factor #Medicine
paper · doi:10.1289/ehp.10724
openalex publication_date 2008/02/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/04
BACKGROUND: Styrene trimers (STs) are polystyrene-container-eluted materials that are sometimes detected in packaged foods. Although the possible endocrine-disrupting effects of STs, such as estrogenic activities, have been reported, their potential thyroid toxicity, such as that caused by the related endocrine disruptor 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has not been studied in detail. OBJECTIVE: Using wild-type and aryl hydrocarbon receptor (Ahr)-null mice, we investigated whether 2,4,6-triphenyl-1-hexene (ST-1), an isomer of STs, influences thyroxin (T(4)) levels in the same manner as TCDD, which induces UDP-glucuronosyltransferase (UGT) via the AhR, resulting in a decrease in T(4) levels in the plasma of mice. METHODS: Both wild-type and Ahr-null mice (five mice per group) were treated for 4 days by gavage with ST-1 (0, 32, or 64 micromol/kg). RESULTS: High-dose (64 micromol/kg) ST-1 decreased the expression of AhR, cytochrome P450 (CYP) 1A1/2, UGT1A1/A6, and CYP2B10 mRNAs and the enzyme activity for CYP1A and UGT1A only in the wild-type mice. This dose decreased AhR DNA binding, but paradoxically increased AhR translocation to the nucleus. In contrast, a high dose of ST-1 increased T(4) levels in the plasma in wild-type mice but did not influence T(4) levels in AhR-null mice. CONCLUSIONS: Although ST-1 treatment might cause an increase in AhR levels in the nucleus by inhibiting AhR export, this chemical down-regulated AhR mRNA, thus leading to down-regulation of AhR target genes and an increase in plasma T(4) levels.