Williams G R
Molecular Endocrinology Group, Division of Medicine & MRC Clinical Sciences Centre, Imperial College, London, UK.
J Neuroendocrinol. 2008 Jun;20(6):784-94. doi: 10.1111/j.1365-2826.2008.01733.x.
For over 100 years, thyroid hormones have been known to be essential for neonatal neurodevelopment but whether they are required by the foetal brain remains a matter of controversy. For decades, the prevailing view was that thyroid hormones are not necessary until after birth because circulating levels in the foetus are very low and the placenta forms an efficient barrier to their transfer from the mother. Clinical observations of good neurological outcome following early treatment of congenital hypothyroidism were used to support the view that thyroid hormones are not required early in neurodevelopment. Nevertheless, the issue remained contentious because of findings that the severity of foetal neurological deficit due to maternal iodine deficiency correlated with the degree of maternal thyroxine (T4) deficiency. Furthermore, neurological damage in these cases could be prevented by correction of maternal T4 deficiency before mid-gestation. This observation led to the opposing view, supported by epidemiological studies of neurological cretinism, that maternal thyroid hormones are important and necessary for early foetal neurodevelopment. It is now clear that thyroid hormones are essential for both foetal and post-natal neurodevelopment and for the regulation of neuropsychological function in children and adults. In recent years, this controversial subject has progressed very rapidly following remarkable progress in understanding of the molecular mechanisms of thyroid hormone action. This article reviews the contributions of molecular biology and genetics to our new understanding of the physiological effects of thyroid hormones on neurodevelopment and in the adult brain.
100多年来，人们一直认为甲状腺激素对新生儿神经发育至关重要，但胎儿大脑是否需要甲状腺激素仍存在争议。几十年来，主流观点是甲状腺激素在出生后才是必需的，因为胎儿体内的循环水平非常低，而且胎盘形成了一道有效的屏障，阻止甲状腺激素从母体转移过来。先天性甲状腺功能减退症早期治疗后神经发育良好的临床观察结果被用来支持甲状腺激素在神经发育早期并非必需的观点。然而，这个问题仍然存在争议，因为有研究发现，母亲碘缺乏导致的胎儿神经缺陷严重程度与母亲甲状腺素（T4）缺乏程度相关。此外，在妊娠中期之前纠正母亲的T4缺乏可以预防这些病例中的神经损伤。这一观察结果导致了相反的观点，即母亲的甲状腺激素对胎儿早期神经发育很重要且是必需的，这一观点得到了神经型克汀病流行病学研究的支持。现在很清楚，甲状腺激素对胎儿和出生后的神经发育以及儿童和成人神经心理功能的调节都至关重要。近年来，随着对甲状腺激素作用分子机制的理解取得显著进展，这个有争议的话题发展非常迅速。本文综述了分子生物学和遗传学对我们对甲状腺激素对神经发育和成年大脑生理作用新认识的贡献。
