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

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.