Styrene trimer may increase thyroid hormone levels via down-regulation of the aryl hydrocarbon receptor (AhR) target gene UDP-glucuronosyltransferase.
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.
Yanagiba
Yukie
Y
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya, Japan.
Ito
Yuki
Y
Yamanoshita
Osamu
O
Zhang
Shu-Yun
SY
Watanabe
Gen
G
Taya
Kazuyoshi
K
Li
Chun Mei
CM
Inotsume
Yuko
Y
Kamijima
Michihiro
M
Gonzalez
Frank J
FJ
Nakajima
Tamie
T
D000475:Alkenes / Q000737:chemistry / Q000633:toxicity*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D004147:Dioxins / Q000633:toxicity; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D011137:Polystyrenes / Q000737:chemistry / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D013730:Terphenyl Compounds / Q000737:chemistry / Q000633:toxicity*; D013963:Thyroid Hormones / Q000097:blood*; D013974:Thyroxine / Q000097:blood
D000475:Alkenes; D004147:Dioxins; D011137:Polystyrenes; D018336:Receptors, Aryl Hydrocarbon; D013730:Terphenyl Compounds; D013963:Thyroid Hormones; C066841:2,3,7,8-tetrabromodibenzo-4-dioxin; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C101679:Cyp2b10 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D000072467:Cytochrome P450 Family 2; D014453:Glucuronosyltransferase; C533342:2,4,6-triphenyl-1-hexene; D013974:Thyroxine