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Environ Health Perspect. 2008 Jun;116(6):740-5. doi: 10.1289/ehp.10724.

Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor (AhR) target gene UDP-glucuronosyltransferase.

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  • 1Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.

Abstract

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.

KEYWORDS:

UDP-glucuronosyltransferase; aryl hydrocarbon receptor; cytochrome P450 1A; styrene trimer; thyroid hormone

PMID:
18560529
PMCID:
PMC2430229
DOI:
10.1289/ehp.10724
[PubMed - indexed for MEDLINE]
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