Syndromes of thyroid hormone resistance

P. Beck-Peccoz, D. Mannavola, L. Persani

Research output: Contribution to journalArticlepeer-review


Thyroid hormone resistance (RTH) is a rare autosomal dominant disorder, characterized clinically by goiter and biochemically by elevated circulating free thyroid hormone levels in the presence of measurable serum TSH concentrations. About 85% of patients with RTH are harboring mutations in thyroid hormone receptor beta (TRβ). These mutations cluster in three different "hot spot" in the T3 binding domain of the receptor. When mapped to their homologous residues in the TR crystal structure, these three clusters of mutations border the T3-binding pocket. As a consequence, most TRβ mutations impair the hormone binding to the receptor and interfere with the mechanism(s) of corepressor release and the consequent recruitβ ment of coactivators. Thus, the remodeling of chromatin structure throughout the process of histone acetylation is prevented and the transcriptional activity of the mutant receptor on both positively and negatively regulated genes, severely disrupted. The lack of interaction with coactivators appears to be an additional mechanism for the dominant negative effects of mutant TRβ on the transcriptional activity of the normal receptor.

Original languageEnglish
Pages (from-to)264-269
Number of pages6
JournalAnnales d'Endocrinologie
Issue number3
Publication statusPublished - Jun 2005


  • Alpha and beta subunits of TSH
  • Coactivators
  • Cofactors
  • Corepressors
  • Gene mutations
  • Thyroid hormone receptor (TR)
  • Thyroid hormone resistance
  • Thyrotropin (TSH) secretion
  • Thyrotropin-releasing hormone (TRH)

ASJC Scopus subject areas

  • Endocrinology


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