Regulation of thyroid hormone action by medium-chain fatty acids

D. C. Thurmond, R. A. Baillie, A. G. Goodridqe

Research output: Contribution to journalArticle

Abstract

Triiodothyronine (T3) causes a 30- to 50-fold increase in transcription of the malic enzyme gene in chick-embryo hepatocytes in culture; mediumchain fatty acids (MCFA's) inhibit this increase. The action of T3 is mediated via thyroid hormone receptors (TR's) which bind to thyroid hormone response elements (T3RE's) in the 5′-flanking DNA of the malic enzyme gene. In previous work from our laboratory, sequences which confer this response on the malic enzyme gene were localized to a T3 response unit between -3903 and -3768 bp upstream of the start site for transcription of the malic enzyme gene. The sequences between -3883 and -3858 bp contain the major functional T3RE of the chicken malic enzyme gene, and this T3RE is complemented by at least six weak T3RE half-sites. Sequence elements that confer inhibition by MCFA co-localized with the TSRE's. When the T3 response unit was linked to a minimal promoter from Herpes Simplex Virus thymidine klnase (HSVTK) and introduced into chick-embryo hepatocytes in culture by transient transfection, T3 caused a 60- to 90-fold increase in chloramphenicol acetyltransferase (CAT) activity. This T3-induced increase in CAT activity was inhibited by 50 to 80% by 1 mM hexanoate. Point mutations and block deletions in each of the T3RE half-sites inhibited promoter activity and resulted in T3-stimulation that varied from 3.5- to 90-fold. Nevertheless, the MCFA-inhibition with each of these constructs was still 50 to 80%. Artificial TSRE's also exhibited MCFA-inhibition. MCFA's inhibited T3-stimulated transcription even when TR was overexpressed, suggesting that the protein which MCFA regulates may not compete with TR for T3RE occupancy. These results are consistent with the hypothesis that MCFA represses T3-induced transcription by inhibiting a function of TR. Supported by Grant DK21594 from the NIH.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number6
StatePublished - 1996
Externally publishedYes

Fingerprint

medium chain fatty acids
triiodothyronine
thyroid hormones
Thyroid Hormones
Fatty Acids
Thyroid Hormone Receptors
malic enzyme
Genes
fatty acids
Transcription
Enzymes
Chloramphenicol O-Acetyltransferase
transcription (genetics)
Chick Embryo
chloramphenicol acetyltransferase
Hepatocytes
genes
hepatocytes
embryo (animal)
Transcription Initiation Site

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Thurmond, D. C., Baillie, R. A., & Goodridqe, A. G. (1996). Regulation of thyroid hormone action by medium-chain fatty acids. FASEB Journal, 10(6).

Regulation of thyroid hormone action by medium-chain fatty acids. / Thurmond, D. C.; Baillie, R. A.; Goodridqe, A. G.

In: FASEB Journal, Vol. 10, No. 6, 1996.

Research output: Contribution to journalArticle

Thurmond, DC, Baillie, RA & Goodridqe, AG 1996, 'Regulation of thyroid hormone action by medium-chain fatty acids', FASEB Journal, vol. 10, no. 6.
Thurmond DC, Baillie RA, Goodridqe AG. Regulation of thyroid hormone action by medium-chain fatty acids. FASEB Journal. 1996;10(6).
Thurmond, D. C. ; Baillie, R. A. ; Goodridqe, A. G. / Regulation of thyroid hormone action by medium-chain fatty acids. In: FASEB Journal. 1996 ; Vol. 10, No. 6.
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AB - Triiodothyronine (T3) causes a 30- to 50-fold increase in transcription of the malic enzyme gene in chick-embryo hepatocytes in culture; mediumchain fatty acids (MCFA's) inhibit this increase. The action of T3 is mediated via thyroid hormone receptors (TR's) which bind to thyroid hormone response elements (T3RE's) in the 5′-flanking DNA of the malic enzyme gene. In previous work from our laboratory, sequences which confer this response on the malic enzyme gene were localized to a T3 response unit between -3903 and -3768 bp upstream of the start site for transcription of the malic enzyme gene. The sequences between -3883 and -3858 bp contain the major functional T3RE of the chicken malic enzyme gene, and this T3RE is complemented by at least six weak T3RE half-sites. Sequence elements that confer inhibition by MCFA co-localized with the TSRE's. When the T3 response unit was linked to a minimal promoter from Herpes Simplex Virus thymidine klnase (HSVTK) and introduced into chick-embryo hepatocytes in culture by transient transfection, T3 caused a 60- to 90-fold increase in chloramphenicol acetyltransferase (CAT) activity. This T3-induced increase in CAT activity was inhibited by 50 to 80% by 1 mM hexanoate. Point mutations and block deletions in each of the T3RE half-sites inhibited promoter activity and resulted in T3-stimulation that varied from 3.5- to 90-fold. Nevertheless, the MCFA-inhibition with each of these constructs was still 50 to 80%. Artificial TSRE's also exhibited MCFA-inhibition. MCFA's inhibited T3-stimulated transcription even when TR was overexpressed, suggesting that the protein which MCFA regulates may not compete with TR for T3RE occupancy. These results are consistent with the hypothesis that MCFA represses T3-induced transcription by inhibiting a function of TR. Supported by Grant DK21594 from the NIH.

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