C Di Cosmo1, X Liao1, AM Dumitrescu1, NJ Philp3, RE Weiss1 and S Refetoff1,2.

Abstract: 

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.