Ahmed R G
Division of Anatomy and Embryology, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
Thyroid Res. 2015 Feb 11;8:2. doi: 10.1186/s13044-015-0013-7. eCollection 2015.
Most of our knowledge on the mechanisms of thyroid hormone (TH) dependent brain development is based on clinical observations and animal studies of maternal/fetal hypothyroidism. THs play an essential role in brain development and hormone deficiency during critical phases in fetal life may lead to severe and permanent brain damage. Maternal hypothyroidism is considered the most common cause of fetal TH deficiency, but the problem may also arise in the fetus. In the case of congenital hypothyroidism due to defects in fetal thyroid gland development or hormone synthesis, clinical symptoms at birth are often mild as a result of compensatory maternal TH supply. TH transporters (THTs) and deiodinases (Ds) are important regulators of intracellular triiodothyronine (T3) availability and therefore contribute to the control of thyroid receptors (TRs)-dependent CNS development and early embryonic life. Defects in fetal THTs or Ds may have more impact on fetal brain since they can result in intracellular T3 deficiency despite sufficient maternal TH supply. One clear example is the recent discovery of mutations in the TH transporter (monocarboxylate transporter 8; MCT8) that could be linked to a syndrome of severe and non reversible psychomotor retardation. Even mild and transient changes in maternal TH levels can directly affect and alter the gene expression profile, and thus disturb fetal brain development. Animal studies are needed to increase our understanding of the exact role of THTs and Ds in prenatal brain development.
我们对甲状腺激素（TH）依赖型脑发育机制的大部分认识基于对母体/胎儿甲状腺功能减退的临床观察和动物研究。甲状腺激素在脑发育中起关键作用，胎儿期关键阶段的激素缺乏可能导致严重且永久性的脑损伤。母体甲状腺功能减退被认为是胎儿甲状腺激素缺乏的最常见原因，但问题也可能出现在胎儿自身。在因胎儿甲状腺发育或激素合成缺陷导致的先天性甲状腺功能减退病例中，由于母体甲状腺激素的代偿性供应，出生时的临床症状往往较轻。甲状腺激素转运体（THTs）和脱碘酶（Ds）是细胞内三碘甲状腺原氨酸（T3）可利用性的重要调节因子，因此有助于控制甲状腺受体（TRs）依赖的中枢神经系统发育和早期胚胎生命。胎儿THTs或Ds的缺陷可能对胎儿大脑有更大影响，因为尽管母体甲状腺激素供应充足，它们仍可能导致细胞内T3缺乏。一个明显的例子是最近发现甲状腺激素转运体（单羧酸转运体8；MCT8）的突变可能与严重且不可逆的精神运动发育迟缓综合征有关。即使母体甲状腺激素水平的轻微和短暂变化也可直接影响并改变基因表达谱，从而干扰胎儿脑发育。需要进行动物研究以增进我们对THTs和Ds在产前脑发育中确切作用的理解。
