A novel role for MCT8: Control of thyroid hormone secretion
The mechanism of thyroid hormone (TH) secretion from the thyroid gland into the blood is unknown. We used the Mct8 deficient mouse (Mct8KO) to determine if MCT8 has a role in this process. While MCT8 is known to transport TH into cells, several observations suggest that it also controls TH secretion: (1) Humans and mice deficient in MCT8 have a low serum T4 level, which cannot be fully explained by increased deiodination; (2) Our preliminary data show that TH secretion in Mct8KO mice is delayed following the release of endogenous hormone suppression with methimazole and perchlorate; (3) MCT8 is localized at the basolateral membrane of thyrocytes. RESULTS: Thyroid glands of Mct8KO mice contained 2.1-fold and 2.3-fold more free T4 and T3 than wild-type (Wt) mice (P<0.001). This was independent of deiodination as comparable increases were also found in Mct8KO mice that lacked the types 1 and 2 deiodinases. Next we determined the rate of iodothyronine secretion in mice thyroid glands after administration of 125I. Peak thyroidal 125I uptake occurred at 8 h in both genotypes. However, in Mct8KO mice there was a significant reduction in the rate of decrease in thyroidal 125I and in the appearance of iodothyronines in serum as TCA-precipitable radioactivity.