Endocrine Abstracts (2008) 16 P737

Role of deiodinases in the thyroid for the maintenance of circulating T3 levels

Jazmin Chiu, Eva Wirth & Ulrich Schweizer


Charité-Universitätsmedizin Berlin, Berlin, Germany.


Deiodinases (Dio1-3) are selenium-dependent enzymes that catalyze the reductive removal of iodine from iodothyronines. Depending on the substrate and the position of the iodine removed, deiodination can generate T3 from T4 or inactivate T3 and T4. Local expression of Dio can help to adjust the intracellular levels of T3 to the physiological needs of the organ without changing circulating T3 concentrations. It has been suggested that hepatic Dio1 generates circulating T3. However, we have shown that mice with a hepatocyte-specific inactivation of selenoprotein expression do not display altered serum T3, T4, or TSH levels (Streckfuss et al. Biochem Biophys Res Comm 2005). In addition, classical gene disruption of Dio1 in the mouse did not reduce circulating T3 values (Schneider et al. Endocrinology 2006). Since Dio2-deficient mice are also not deficient in circulating T3 levels, the question for the source of circulating T3 remains open. Since Dios are expressed in the thyroid, we speculated that T3 may also be produced intrathyroidally by 5′-deiodination of T4. In order to investigate this possibility, we have generated mice with a tamoxifen-inducible inactivation of selenoprotein-specific tRNA (gene symbol Trsp) in thyrocytes: Tg-CreER; Trspfl/fl mice. Application of tamoxifen resulted in a significant decrease of thyroidal Dio1 activity providing a model in which to study the role of intrathyroidal deiodinase activity for circulating T3 levels. In pilot experiments, we observed a reduction of plasma T3 levels in these mice. Thus, it may be possible that thyroidal Dio directly contribute to circulating T3 levels. This notion is compatible with reports on physiological variations of the T3/T4 ratio released from the thyroid gland under conditions of stimulation of the TSH receptor by TSH or TSHr autoantibodies or during severe iodine deficiency. Supported by DAAD and DFG grants.

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