TY  - JOUR
A1  - Schraplau, Anne
A1  - Schewe, Bettina
A1  - Neuschäfer-Rube, Frank
A1  - Ringel, Sebastian
A1  - Neuber, Corinna
A1  - Kleuser, Burkhard
A1  - Püschel, Gerhard Paul
T1  - Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital
JF  - Toxicology
N2  - Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
KW  - Endocrine disruption
KW  - Xenobesity
KW  - Aryl-hydrocarbon receptor
KW  - Cyp2b1
KW  - Thyroid hormone
KW  - UDP-glucuronosyltransferase
Y1  - 2015
U6  - https://doi.org/10.1016/j.tox.2014.12.004
SN  - 0300-483X
VL  - 328
SP  - 21
EP  - 28
PB  - Elsevier
CY  - Clare
ER  -