Abstract
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.
Footnotes
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This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.106.112706.
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ABBREVIATIONS: PB, phenobarbital; CAR, constitutive active/androstane receptor; PH, partial hepatectomy; TCPOBOP, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene; KO, knockout; P450, cytochrome P450; CPT-1, carnitine palmitoyl transferase 1; T4, tetraiodothyronine; D1, type 1 deiodinase; D2, type 2 deiodinase; D3, type 3 deiodinase; T3, triiodothyronine; rT3, reverse triiodothyronine; PCR, polymerase chain reaction; TAT, tyrosine aminotransferase; BTEB, basic transcription element binding protein; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; ELISA, enzyme-linked immunosorbent assay; TSH, thyroid-stimulating hormone.
- Received August 21, 2006.
- Accepted October 17, 2006.
- The American Society for Pharmacology and Experimental Therapeutics
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