The Nuclear Receptor Constitutively Active/Androstane Receptor Regulates Type 1 Deiodinase and Thyroid Hormone Activity in the Regenerating Mouse Liver

摘要

We observed that the level of reverse triiodothyronine (rT3) was significantly increased after partial hepatectomy (PH) in both wild-type and constitutively active/androstane receptor (CAR) knockout (KO) mice,and treatment with phenobarbital (PB),a CAR activator,after PH decreased rT3 to restore its original level only in wild-type mice.On the other hand,no significant changes in the level of total T3 or free T3 in the serum were observed in either wild-type or CAR KO mice after PH or treatment with PB.Type 1 deiodinase (D1) activity and expression were significantly reduced by PH and up-regulated by PB in a CAR-dependent manner.In addition,known T3-regulated genes [tyrosine aminotransferase (TAT) and basic transcription element binding protein (BTEB)] were also significantly decreased by PH and induced by PB.Injection of rT3 into normal mice revealed that rT3 is capable of repressing the known thyroid hormone-regulated genes Tat,Bteb,and Cpt-1 in the liver.Our results suggest that PH decreases D1 activity leading to increased rT3 level,resulting in the repression of T3 target genes.Subsequent treatment with PB decreases rT3 in a CAR-dependent manner through the up-regulation of the D1 gene.