The Challenges and Complexities of Thyroid Hormone Replacement

Shayri M. Kansagra, BS; Christopher R. McCudden, PhD; Monte S. Willis, MD, PhD


Lab Med. 2010;41(6):229-348. 

In This Article

Thyroid Hormone Receptors and Molecular Signaling in the Brain

Thyroid hormones signal through nuclear thyroid hormone receptors THR-α and THR-β as both homodimers and heterodimers. Hormone-receptor complexes bind to thyroid hormone response elements (THREs) in the promoter region of target genes, which are then transcribed (Figure 4).[62,63] In the brain, THR-α1 is the most highly expressed nuclear thyroid receptor; 70%–80% of T3 binds to THR-α1.[64] Despite its widespread distribution in neural tissue, deletion of all of the thyroid hormone receptors in the brain does not produce a typical hypothyroid phenotype. This suggests that the lack of T3 has worse consequences than the lack of THRs (reviewed by Forrest and Vennstrom, 2000,[65] Bernal, 2007,[66] O'Shea and Williams, 2002,[67] and Flamant and Samarut, 2003.[63]) It also supports thyroid hormone bioactivity that is not dependent on canonical thyroid hormone receptors.