Abstract
Thyroid hormone receptor mutations cause syndromes of resistance to the
action of thyroid hormones (RTH) with autosomal dominant inheritance. Mutations in
the THRA gene, encoding TRα1 and TRα2, cause RTHα, and those in THRB, encoding
TRβ1 and TRβ2, cause RTHβ. In RTHα, relatively mild changes in circulating thyroid
hormones coexist with signs of congenital hypothyroidism. In contrast, in RTHβ, TSH
levels are not suppressed despite elevated thyroid hormone levels. The mutant
receptors have low or no T3-induced activation and display dominant negative activity,
inhibiting the wild-type receptors’ transcriptional activation. This chapter describes the
main characteristics of RTH, including a discussion of the mouse models of the
disorder, with an emphasis on neural aspects.
