SFEBES2016 Plenary Lectures British Thyroid Association Pitt-Rivers Lecture (1 abstracts)
London.
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.