Enhanced Phenobarbital-induced Thyroid Hormone Breakdown in Hepatocytes by Benzo[a]pyren-dependent Induction of the Constitutive Androstane Receptor

Introduction: Xenobiotic exposure has been discussed as a possible contributor to the obesity epidemic. Amongst others, xenobiotics may reduce the metabolic rate because they interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones. This induction results from an activation of xeno-sensing nuclear receptors in the liver. The Constitutive Androstane Receptor (CAR, NR1I3) is a xenobiotic-responsive nuclear receptor, which is also involved in the energy homeostasis regulation. The activation of CAR and its target genes leads to an enhanced hepatic thyroid…