Developmental roles of the thyroid hormone receptor α and β genes

Abstract

Publisher Summary This chapter discusses the developmental roles of the thyroid hormone (TH) receptor α and β genes. A feature of thyroid hormone receptor (TR) signaling is its adaptability and is illustrated in two developmental processes: (1) hearing exemplifies a complex function that is subject to multiple levels of control by thyroid hormone in different cell types in the auditory system and (2) the color visual system is unexpectedly dependent on TR signaling but unlike the auditory system, this largely centers around the differentiation of a single cell type, the cone photoreceptor. Thyroid hormone (T3) has numerous actions in development in vertebrate species. TRs that act as T3-regulated transcription factors are central to these actions. Several TRα and TRβ isoforms encoded by two genes (Thra and Thrb) provide biological versatility. Gene targeting has indicated specific roles for each gene—for example, Thra determines heart rate, thermogenesis, and bone and intestinal differentiation, whereas Thrb controls the pituitary–thyroid axis and liver function. Thrb is also critical for hearing and color vision. Together, Thra and Thrb coregulate a wider spectrum of actions in brain function, growth, and fertility. The deletion of all α and β receptors results in viable mice, but these exhibit immaturity in multiple systems, indicating the importance of T3 signaling at the later, maturational stages of development. The tissue specificity and timing of TR functions in vivo are likely to be determined in cooperation with other factors, including deiodinase enzymes that regulate hormone availability in a given tissue.