Thyroid hormone transporters in health and disease: advances in thyroid hormone deiodination

Thyroid hormone metabolism by the three deiodinase selenoproteins – DIO1, DIO2, and DIO3 – regulates the local availability of various iodothyronine metabolites and thus mediates their effects on gene expression, thermoregulation, energy metabolism, and many key reactions during the development and maintenance of an adult organism. Circulating serum levels of thyroid hormone and thyroid-stimulating hormone, used as a combined indicator of thyroid hormone status, reflect a composite picture of: thyroid secretion; tissue-specific production of T₃ by DIO1 and DIO2 activity, which both contribute to circulating levels of T₃; and degradation of the prohormone T4, of the thyromimetically active T₃, of the inactive rT₃, of other iodothyronines metabolites with a lower iodine content and of thyroid hormone conjugates. Degradation reactions are catalyzed by either DIO1 or DIO3. Aberrant expression of individual deiodinases in disease, single nucleotide polymorphisms in their genes, and novel regulators of DIO gene expression (such as bile acids) provide a more complex picture of the fine tuning and the adaptation of systemic and local bioavailability of thyroid hormones.

Key words: bile acid, deiodinase, diabetes, feedback regulation, hypothalamic regulation, insulin resistance, iodothyronine, selenoprotein, sulfation, T₃ transporter, thermogenesis, thyronamine, TSH set-point