Regulation of the action of steroid/thyroid hormone receptors by medium- chain fatty acids

Debbie C. Thurmond, Rebecca A. Baillie, Alan G. Goodridge

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Triiodothyronine (T3) causes a 30-fold increase in transcription of the malic enzyme gene in chick embryo hepatocytes; medium-chain fatty acids (MCFAs) inhibit this increase. T3 action is mediated by T3 receptors (TRs) that bind to T3 response elements (T3RFs) in this gene's 5'-flanking DNA. In transiently transfected hepatocytes, fragments of 5'-flanking DNA of the malic enzyme gene or artificial TsREs that conferred T3 stimulation also conferred MCFA inhibition to linked reporter genes. Thus, MCFA inhibition may be mediated through cisacting T3REs and trans-acting TRs, distinguishing MCFA action from that of other fatty acids which act through unique sequence elements. Using binding assays and overexpression of TR, we showed that MCFAs inhibited the transactivating but not the silencing function of TR and did not alter binding of T3 to TR or of TR to T3RE. The C-terminal ligand- binding domain of TR was sufficient to confer stimulation by T3, but not inhibition by MCFA. Inhibition of transactivation by MCFA was specific: ligand-stimulated transcription from T3 or estrogen response elements was inhibited, but that from glucocorticoid or cyclic AMP response elements was not. We propose that MCFAs or metabolites thereof influence the activity of a factor(s) that interacts with the T3 and estrogen receptors to inhibit ligand-stimulated transcription.

Original languageEnglish (US)
Pages (from-to)15373-15381
Number of pages9
JournalJournal of Biological Chemistry
Volume273
Issue number25
DOIs
StatePublished - Jun 19 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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