Piosik P A, van Groenigen M, Baas F
Department of Neurology, Academic Medical Center, University of Amsterdam, The Netherlands.
Brain Res Mol Brain Res. 1996 Dec;42(2):227-35. doi: 10.1016/s0169-328x(96)00126-x.
Thyroid hormone deficiency has profound effects on the brain during development and less marked effects on the adult brain. These effects are considered to be the result of the direct regulation of specific target genes by thyroid hormone. Previous studies have shown that the expression of the neuronal gene RC3, encoding a 78-amino-acid calmodulin-binding protein kinase C substrate, is under the influence of thyroid hormone in vivo. In congenitally hypothyroid foetal goat at term (approximately 150 days of gestation), RC3 mRNA expression was reversibly decreased in the striatum but not in other brain regions. In the present study we investigated the role of thyroid hormone in RC3 mRNA expression at earlier stages of fetal development and in mature goats using in situ hybridization. There was a consistent decrease (35-80%) in the signal for RC3 mRNA per neuron in the striatum of hypothyroid adult and fetal goats of 90, 120 and 150 days of gestation compared to normal goats of the same age. In contrast, no consistent difference was observed in the cerebral cortex at any age studied. These data indicate that in both fetal and adult goats thyroid hormone, at least partly, affects the expression of RC3 mRNA in the striatum and not the cerebral cortex.
甲状腺激素缺乏在发育过程中对大脑有深远影响，而对成人大脑的影响则不那么明显。这些影响被认为是甲状腺激素直接调控特定靶基因的结果。先前的研究表明，编码一种78个氨基酸的钙调蛋白结合蛋白激酶C底物的神经元基因RC3的表达在体内受甲状腺激素影响。在足月先天性甲状腺功能减退的胎羊（妊娠约150天）中，纹状体中RC3 mRNA表达可逆性降低，但在其他脑区未降低。在本研究中，我们使用原位杂交技术研究了甲状腺激素在胎儿发育早期和成年山羊中对RC3 mRNA表达的作用。与相同年龄的正常山羊相比，90、120和150天妊娠的甲状腺功能减退成年和胎羊纹状体中每个神经元的RC3 mRNA信号持续下降（35-80%）。相比之下，在所研究的任何年龄的大脑皮质中均未观察到一致的差异。这些数据表明，在胎儿和成年山羊中，甲状腺激素至少部分影响纹状体而非大脑皮质中RC3 mRNA的表达。
