Thyroid Hormone Receptors in the Brain: Distribution and Deletion Effects on Brain Structure and Behavior

The thyroid hormone receptors, encoded by the THRA and THRB genes, transduce the actions of T3. Receptor expression analysis gave clues on thyroid hormone and receptor functions in specific brain regions or cell types. This chapter describes the studies performed on rodents on receptor expression by various methodologies, including in situ hybridization and the phenotype of Thra and Thrb knockout mice. Most brain regions express the receptors from fetal stages. Receptor expression studies on rodents indicate that thyroid hormones regulate neuronal migration and differentiation during neocortical and cerebellar development. Given the critical role of thyroid hormones in brain development, it was expected that disruption of the receptor genes would be equivalent to hormone deprivation. However, in many cases, this is not so, raising the question of the role of unliganded receptor activity in hypothyroidism. This chapter ends with the few available data on receptor expression in the human fetal brain.