RT Journal Article
SR Electronic
T1 The Nuclear Receptor Constitutively Active/Androstane Receptor Regulates Type 1 Deiodinase and Thyroid Hormone Activity in the Regenerating Mouse Liver
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 307
OP 313
DO 10.1124/jpet.106.112706
VO 320
IS 1
A1 Tien, Eric S.
A1 Matsui, Kenji
A1 Moore, Rick
A1 Negishi, Masahiko
YR 2007
UL http://jpet.aspetjournals.org/content/320/1/307.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics