Silva J E, Rudas P
Thyroid Unit, Brigham and Women's Hospital, Boston, Massachusetts.
Endocrinology. 1990 Feb;126(2):1276-82. doi: 10.1210/endo-126-2-1276.
In view of the defective neurotubule assembly observed in congenital hypothyroidism and the striking morphological abnormalities of the cerebellum in this condition, we have investigated the expression of microtubule-associated protein-2 (MAP2) in the cerebellum of rats with congenital hypothyroidism. Analysis included the measurement of immunoreactive MAP2 and its mRNA. In addition, the intracellular distribution of MAP2 was studied by immunostaining of the appropriate histological preparations. The results showed that the developmental increase in MAP2 is delayed in congenital hypothyroidism, but eventually the concentration of this protein reached normal levels in animals with this condition, even if untreated. These abnormalities in the immunoreactive protein are not paralleled by abnormalities in the abundance of MAP2 mRNA, which was not affected by the thyroid status of the animals. In spite of the normalization of the content of the protein, the distribution of MAP2 in the Purkinje cells of hypothyroid rats remained abnormal. Whereas in euthyroid rats the protein rapidly migrated into the dendrites, in the Purkinje cells of hypothyroid pups, MAP2 remained largely confined to the body and the most proximal part of the dendrites. These results suggest that thyroid hormone affects the expression of MAP2 at translation or posttranslational levels. The abnormality in distribution may result from some posttranslational abnormality of the protein itself or some underlying defect in the function of the neurons. These observations are probably relevant to the abnormalities in cerebellar function seen in animals and humans with untreated congenital hypothyroidism.
鉴于在先天性甲状腺功能减退症中观察到的神经微管组装缺陷以及该病症中小脑明显的形态学异常，我们研究了先天性甲状腺功能减退症大鼠小脑微管相关蛋白2（MAP2）的表达。分析包括免疫反应性MAP2及其mRNA的测定。此外，通过对合适的组织学标本进行免疫染色研究了MAP2的细胞内分布。结果表明，先天性甲状腺功能减退症中MAP2的发育性增加延迟，但最终即使未经治疗，该蛋白质在患有这种病症的动物体内浓度也达到正常水平。免疫反应性蛋白质的这些异常与MAP2 mRNA丰度的异常并不平行，后者不受动物甲状腺状态的影响。尽管蛋白质含量恢复正常，但甲状腺功能减退大鼠浦肯野细胞中MAP2的分布仍保持异常。在甲状腺功能正常的大鼠中，该蛋白质迅速迁移到树突中，而在甲状腺功能减退幼崽的浦肯野细胞中，MAP2主要局限于细胞体和树突的最近端部分。这些结果表明，甲状腺激素在翻译或翻译后水平影响MAP2的表达。分布异常可能是由于蛋白质本身的一些翻译后异常或神经元功能的某些潜在缺陷所致。这些观察结果可能与未经治疗的先天性甲状腺功能减退症动物和人类中所见的小脑功能异常有关。
