AP-1 antagonizes thyroid hormone receptor action on the thyrotropin β- subunit gene

F. E. Wondisford, H. J. Steinfelder, M. Nations, S. Radovick

Research output: Contribution to journalArticlepeer-review

Abstract

Thyrotropin-releasing hormone (TRH) stimulates and thyroid hormone (T3) inhibits transcription of the thyrotropin β-subunit gene (TSH-β). The first exon contains DNA sequences necessary for both responses and binds both AP-1 and thyroid hormone receptor (T3R). T3 did not inhibit TSH-β gene expression in a T3R-deficient cell line. Transfection of a T3R expression vector, however, resulted in a 70% inhibition of expression by T3, which was abolished by cotransfection of c-jun and c-fos expression vectors. Mutations surrounding the transcription initiation site and DNA binding studies demonstrate both a functional and structural interaction between c-jun and T3R. Thus, TRH, acting through AP-1, may alter the set point and magnitude of thyroid hormone negative feedback of the TSH-β gene through an interaction between AP-1 and T3R. Other regulatory pathways acting through AP-1 may alter thyroid hormone action in man.

Original languageEnglish (US)
Pages (from-to)2749-2754
Number of pages6
JournalJournal of Biological Chemistry
Volume268
Issue number4
StatePublished - 1993

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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