Hypothyroidism and brain developmental players.
Hypothyroidism and brain developmental players.
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DOI：
10.1186/s13044-015-0013-7
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发表时间：
2015
期刊：
影响因子：
2.2
通讯作者：
Ahmed RG
中科院分区：
文献类型：
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作者：
Ahmed RG
我们对甲状腺激素（TH）依赖性脑发育机制的认识大多是基于对母体/胎儿甲状腺功能减退症的临床观察和动物研究。TH在大脑发育中起着至关重要的作用，在胎儿生命的关键阶段，激素缺乏可能导致严重和永久性的脑损伤。母亲甲状腺功能减退被认为是胎儿TH缺乏的最常见原因，但问题也可能出现在胎儿身上。在由于胎儿甲状腺发育或激素合成缺陷引起的先天性甲状腺功能减退症的情况下，由于母体TH的代偿性供应，出生时的临床症状通常是轻微的。TH转运体（THTs）和脱碘酶（Ds）是细胞内三碘甲状腺原氨酸（T3）利用率的重要调节剂，因此有助于控制甲状腺受体（TRs）依赖的CNS发育和早期胚胎生命。胎儿THT或Ds的缺陷可能对胎儿脑有更大的影响，因为它们可以导致细胞内T3缺乏，尽管母体TH供应充足。一个明显的例子是最近发现的突变TH转运蛋白（单羧酸转运蛋白8; MCT 8），可能与严重和不可逆的精神发育迟滞综合征。即使是轻微的和短暂的变化，母亲TH水平可以直接影响和改变基因表达谱，从而干扰胎儿脑发育。需要动物研究来增加我们对THT和Ds在产前脑发育中的确切作用的理解。
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.