Thyroid hormone (T3) inhibits ciprofibrate-induced transcription of genes encoding β-oxidation enzymes: Cross talk between peroxisome proliferator and T3 signaling pathways

Ruiyin Chu, Laird D. Madison, Yulian Lin, Peter Kopp, M. Sambasiva Rao, J. Larry Jameson, Janardan K. Reddy*

*Corresponding author for this work

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

Peroxisome proliferators cause rapid and coordinated transcriptional activation of genes encoding peroxisomal β-oxidation system enzymes by activating peroxisome proliferator-activated receptor (PPAR) isoform(s). Since the thyroid hormone (T3; 3,3',5-triiodothyronine) receptor (TR), another member of the nuclear hormone receptor superfamily, regulates a subset of fatty acid metabolism genes shared with PPAR, we examined the possibility of interplay between peroxisome proliferator and T3 signaling pathways. T3 inhibited ciprofibrate-induced luciferase activity as well as the endogenous peroxisomal β-oxidation enzymes in transgenic mice carrying a 3.2-kb 5'-flanking region of the rat peroxisomal enoyl-CoA hydratase/3- hydroxyacyl-CoA dehydrogenase gene fused to the coding region of luciferase. Transfection assays in hepatoma H4-II-E-C3 and CV-1 cells indicated that this inhibition is mediated by TR in a ligand-dependent fashion. Gel shift assays revealed that modulation of PPAR action by TR occurs through titration of limiting amounts of retinoid X receptor (RXR) required for PPAR activation. Increasing amounts of RXR partially reversed the inhibition in a reciprocal manner; PPAR also inhibited TR activation. Results with heterodimerization- deficient TR and PPAR mutants further confirmed that interaction between PPAR and TR signaling systems is indirect. These results suggest that a convergence of the peroxisome proliferator and T3 signaling pathways occurs through their common interaction with the heterodimeric partner RXR.

Original languageEnglish (US)
Pages (from-to)11593-11597
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number25
DOIs
StatePublished - Dec 5 1995

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Thyroid hormone (T<sub>3</sub>) inhibits ciprofibrate-induced transcription of genes encoding β-oxidation enzymes: Cross talk between peroxisome proliferator and T<sub>3</sub> signaling pathways'. Together they form a unique fingerprint.

  • Cite this