Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion
Mice deficient in MCT8 reveal a mechanism regulating thyroid hormone secretion
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DOI：
10.1172/jci42113
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发表时间：
2010-09-01
影响因子：
15.9
通讯作者：
Refetoff, Samuel
中科院分区：
文献类型：
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作者：
Di Cosmo, Caterina;Liao, Xiao-Hui;Refetoff, Samuel
甲状腺激素（TH）从甲状腺分泌进入血液的机制尚不清楚。缺乏单羧酸转运体8 （MCT8）的人和小鼠血清甲状腺素（T-4）水平低，这不能完全由脱碘增加来解释。在这里，我们已经证明Mct8定位于甲状腺细胞的基底外膜，并且Mct8- ko小鼠在停止几乎完全耗尽甲状腺TH的治疗后早期血清TH浓度降低。Mct8-KO小鼠的甲状腺比野生型小鼠含有更多的非甲状腺球蛋白相关的T-4和三碘甲状腺原氨酸，不依赖于脱碘。此外，碘缺乏时甲状腺TH含量的消耗较慢。注射I-125后，Mct8-KO小鼠甲状腺分泌I-125的速度和血清中以三氯乙酸可沉淀放射性的形式出现的速度都大大降低。同样，三碘甲状腺原氨酸抑制内源性TSH和T-4的Mct8-KO中，注射促甲状腺素诱导的T-4分泌减少。据我们所知，本研究首次证明Mct8参与甲状腺TH的分泌，并在一定程度上导致Mct8缺乏患者的低血清T-4水平。
The mechanism of thyroid hormone (TH) secretion from the thyroid gland into blood is unknown. Humans and mice deficient in monocarboxylate transporter 8 (MCT8) have low serum thyroxine (T-4) levels that cannot be fully explained by increased deiodination. Here, we have shown that Mct8 is localized at the basolateral membrane of thyrocytes and that the serum TH concentration is reduced in Mct8-KO mice early after being taken off a treatment that almost completely depleted the thyroid gland of TH. Thyroid glands in Mct8-KO mice contained more non-thyroglobulin-associated T-4 and triiodothyronine than did those in wild-type mice, independent of deiodination. In addition, depletion of thyroidal TH content was slower during iodine deficiency. After administration of I-125, the rate of both its secretion from the thyroid gland and its appearance in the serum as trichloroacetic acid-precipitable radioactivity was greatly reduced in Mct8-KO mice. Similarly, the secretion of T-4 induced by injection of thyrotropin was reduced in Mct8-KO in which endogenous TSH and T-4 were suppressed by administration of triiodothyronine. To our knowledge, this study is the first to demonstrate that Mct8 is involved in the secretion of TH from the thyroid gland and contributes, in part, to the low serum T-4 level observed in MCT8-deficient patients.