Evans I M, Pickard M R, Sinha A K, Leonard A J, Sampson D C, Ekins R P
Division of Molecular Endocrinology, University College London Medical School, Mortimer Street, London W1N 8AA, UK.
J Endocrinol. 2002 Dec;175(3):597-604. doi: 10.1677/joe.0.1750597.
Maternal hypothyroidism during pregnancy impairs brain function in human and rat offspring, but little is known regarding the influence of maternal hyperthyroidism on neurodevelopment. We have previously shown that the expression of neuronal and glial differentiation markers in fetal brain is compromised in hypothyroid rat dam pregnancies and have now therefore extended this investigation to hyperthyroid rat dams. Study groups comprised partially thyroidectomised dams, implanted with osmotic pumps infusing either vehicle (TX dams) or a supraphysiological dose of thyroxine (T4) (HYPER dams), and euthyroid dams infused with vehicle (N dams). Cytoskeletal protein abundance was determined in fetal brain at 21 days of gestation by immunoblot analysis. Relative to N dams, circulating total T4 levels were reduced to around one-third in TX dams but were doubled in HYPER dams. Fetal brain weight was increased in HYPER dams, whereas litter size and fetal body weight were reduced in TX dams. Glial fibrillary acidic protein expression was similar in HYPER and TX dams, being reduced in both cases relative to N dams. alpha-Internexin (INX) abundance was reduced in HYPER dams and increased in TX dams, whereas neurofilament 68 (NF68) exhibited increased abundance in HYPER dams. Furthermore, INX was inversely related to - and NF68 directly related to - maternal serum total T4 levels, independently of fetal brain weight. In conclusion, maternal hyperthyroidism compromises the expression of neuronal cytoskeletal proteins in late fetal brain, suggestive of a pattern of accelerated neuronal differentiation.
孕期母亲甲状腺功能减退会损害人类和大鼠后代的脑功能，但关于母亲甲状腺功能亢进对神经发育的影响却知之甚少。我们之前已经表明，甲状腺功能减退的大鼠母体妊娠时，胎脑神经元和胶质细胞分化标志物的表达会受到影响，因此我们现在将这项研究扩展到甲状腺功能亢进的大鼠母体。研究组包括部分甲状腺切除的母体，分别植入输注赋形剂的渗透泵（TX母体）或超生理剂量的甲状腺素（T4）（HYPER母体），以及输注赋形剂的甲状腺功能正常的母体（N母体）。通过免疫印迹分析测定妊娠21天时胎脑中细胞骨架蛋白的丰度。相对于N母体，TX母体循环总T4水平降至约三分之一，而HYPER母体则增加了一倍。HYPER母体的胎脑重量增加，而TX母体的窝仔数和胎儿体重减少。HYPER和TX母体中胶质纤维酸性蛋白的表达相似，相对于N母体，两者均降低。α-中间丝蛋白（INX）丰度在HYPER母体中降低，在TX母体中增加，而神经丝68（NF68）在HYPER母体中丰度增加。此外，INX与母体血清总T4水平呈负相关，NF68与母体血清总T4水平呈正相关，且与胎脑重量无关。总之，母亲甲状腺功能亢进会损害晚期胎脑中神经元细胞骨架蛋白的表达，提示神经元分化加速的模式。
