Endocrine Abstracts

Thyroid hormone action in individual target tissues is a complex and tightly regulated process. Thyroid hormones (thyroxine, T₄ and triiodothyronine, T₃) enter target cells via active transport mediated by specific transporter proteins. T₄ is a biologically inactive pro-hormone that is converted to the active hormone T₃ by removal of a critical iodine atom. Two iodothyronine deiodinase enzymes (Dio2 and Dio3) are expressed in peripheral tissues; Dio2 is an activating enzyme that converts T₄ to T₃ whereas Dio3 inactivates both T₄ and T₃ by generating inactive metabolites. The relative activities of Dio2 and Dio3 thus regulate the intracellular availability of T₃. T₃ enters the nucleus and binds with high affinity to nuclear thyroid hormone receptors (TRs) that activate hormone-dependent target gene expression. Thyroid hormone action in individual target cells may be adjusted locally by tissue-specific regulation of thyroid hormone transporter, deiodinase and receptor expression. In studies focusing on the skeleton as an archetypal and physiologically important T₃ target tissue, we show that thyroid hormones exert diverse responses in vivo that are restricted in time and space during development and in adulthood, and which also interact with other endocrine signalling pathways.