[Structure-function relationship of thyroid hormone receptor and analysis of its physiological role by gene targeting]

Abstract

Thyroid hormone plays important role in growth, development and maintenance of homeostasis through regulation of the expression of its target genes. The receptor of thyroid hormone belongs to the superfamily of nuclear hormone receptors, and there are two isotype receptors, alpha and beta, encoded by two distinct homologous genes. Molecular dissection and crystalographical analysis clarified the detailed structure-function relationship of the receptor such as DNA binding, dimerization, hormone binding, and interaction with transcription factors, leading to the understanding of the mechanism of regulation of transcription by thyroid hormone receptor. Furthermore, gene targeting revealed the physiological functions of the alpha and beta thyroid hormone receptor isotypes.