| First Author | Selmi-Ruby S | Year | 2014 |
| Journal | Endocrinology | Volume | 155 |
| Issue | 2 | Pages | 635-46 |
| PubMed ID | 24265449 | Mgi Jnum | J:208718 |
| Mgi Id | MGI:5564862 | Doi | 10.1210/en.2013-1435 |
| Citation | Selmi-Ruby S, et al. (2014) The targeted inactivation of TRbeta gene in thyroid follicular cells suggests a new mechanism of regulation of thyroid hormone production. Endocrinology 155(2):635-46 |
| abstractText | Thyroid epithelial cells, or thyrocytes, express functional thyroid hormone receptors but no precise role has yet been assigned to either TRalpha or TRbeta in the thyroid gland. In this study, we analyzed the impact of inactivating the TRbeta gene in the thyroid of mice. First, we generated a mouse line named Thyr-Cre, expressing the Cre recombinase under the control of the thyroglobulin gene promoter, which led to a complete recombination of floxed genes in thyrocytes. Thyr-Cre mice were then crossed with TRbeta floxed mice (TRbeta(flox/flox)) to obtain a thyrocyte-selective deletion of TRbeta. Thyr-TRbeta(-/-) mice were characterized by a decrease in the size and functional activity of the thyroid gland. These alterations were associated with a decrease in plasma TSH concentration. Surprisingly, Thyr-TRbeta(-/-) displayed elevated serum T(4) and rT(3) concentrations with no significant change in serum T(3) levels. Their intrathyroidal free T(4) and rT(3) contents were also elevated, whereas the ratio of serum T(4) to thyroid free T(4) was decreased by comparison with wild-type littermates. Also, within the thyroid, deiodinases D1 and D2 were reduced as well as the expression levels of genes encoding monocarboxylate transporters (Mct8 and Mct10). Such a decrease in intrathyroidal deiodination of T(4) and in the expression of genes encoding thyroid hormone transporters may contribute to the primary overproduction of T(4) observed in Thyr-TRbeta(-/-) mice. In conclusion, these data show that the control of thyroid hormone production involves not only TRbeta-dependent mechanisms acting at the level of hypothalamus and pituitary but also TRbeta-dependent mechanisms acting at the thyroid level. |
