Molecular Pathogenesis of Resistance to Thyroid Hormone

  • V. K. K. Chatterjee
Part of the Endocrine Updates book series (ENDO, volume 22)


The synthesis of thyroid hormones is controlled by hypothalamic thyrotropin releasing hormone (TRH) and pituitary thyroid stimulating hormone (TSH), and in turn, T4 and T3 regulate TRH and TSH production as part of a negative feedback loop. The feedback effects of thyroid hormones on TSH production are mediated by inhibition of hypothalamic TRH and pituitary TSHα and β subunit gene expression. Target genes which are induced by thyroid hormone include malic enzyme and sex- hormone binding globulin (SHBG) in the liver, myosin heavy chain and sodium-calcium ATP-ase in myocardium, myelin basic protein in brain and sodium-potassium ATP-ase in skeletal muscle. The regulation of these genes by thyroid hormone is mediated by a protein which is a member of the steroid/nuclear receptor superfamily of ligand-inducible transcription factors (1). In keeping with other members of the superfamily, the thyroid hormone receptor (TR) is organized into distinct functional domains. A central DNA binding domain (DBD) containing two “zinc finger” motifs, mediates receptor binding to specific regulatory DNA sequences or thyroid response elements (TREs), usually located in the promoter regions of target genes. Many TREs consist of a tandem or direct repeat arrangement of the hexanucleotide sequence AGGTCA.


Thyroid Hormone Thyroid Stimulate Hormone Thyrotropin Release Hormone Thyroid Hormone Receptor Dominant Negative Inhibition 
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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • V. K. K. Chatterjee
    • 1
  1. 1.Department of Medicine, Addenbrooke’s HospitalUniversity of CambridgeCambridgeUK

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