Department of Endocrine and Nervous System Pathophysiology, Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad Autónoma de Madrid (UAM), E-28029 Madrid, Spain.
Department of Endocrine, U-708, Center for Biomedical Research on Rare Diseases (Ciberer), Instituto de Salud Carlos III, E-28029 Madrid, Spain.
Cereb Cortex. 2018 May 1;28(5):1783-1793. doi: 10.1093/cercor/bhx088.
Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.
甲状腺激素（THs，T4 和转录活性激素 T3）在神经发育中发挥着重要作用；然而，T3 在小鼠胎儿发育期间进入大脑的机制尚不清楚。本研究使用生化、解剖和分子方法探讨了 T3 在小鼠胎儿发育期间进入大脑的来源。研究结果表明，在妊娠后期，大量胎儿大脑 T4 来自母体。此外，在发育中的小鼠大脑中，T4 通过 D2 活性转化为 T3 来调节胎儿 T3 含量，这种活性存在于更早的产前阶段。此外，D2 活性对于调节大脑皮层中 T3 依赖基因的表达至关重要，对于缺乏 TH 转运蛋白单羧酸转运蛋白 8 的小鼠中存在的短暂大脑皮层甲状腺功能亢进也是必需的。值得注意的是，编码 D2（Dio2）的基因主要在血脑屏障（BCSFB）处表达。总的来说，这些数据表明，D2 脱碘的 T4 可能是新皮层发育过程中 T3 的唯一来源。因此，我们提出 BCSFB 处的 D2 活性将穿过脉络丛运输的 T4 转化为 T3，从而为大脑提供活性激素以维持 TH 平衡。
