Lorenzo Petra I, Ménard Catherine, Miller Freda D, Bernal Juan
Instituto de Investigaciones Biomédicas "Alberto Sols,", CSIC, 28029 Madrid, Spain.
Mol Cell Neurosci. 2002 Mar;19(3):333-43. doi: 10.1006/mcne.2001.1087.
Thyroid hormone (T3) is essential for brain development and most of its actions are exerted at the gene expression level after interaction with nuclear receptors. In particular, genes encoding cytoskeletal proteins are influenced by the thyroidal status. Thyroid hormone is involved in the normal downregulation of the Talpha1 alpha-tubulin gene during postnatal growth. The action of T3 on Talpha1 tubulin expression is complex and is exerted at least at two levels. In cultured cells, T3 induces a transient and fast decrease of Talpha1 mRNA concentration. This effect is enhanced when transcription is blocked by actinomycin D, suggesting that T3 increases mRNA degradation. In transgenic animals T3 affects the expression of beta-galactosidase under control of the Talpha1 promoter in the same way as the endogenous gene, supporting an effect mediated through the Talpha1 promoter. However, the Talpha1 promoter is not regulated by T3 in transfected cells and, therefore, the effects of the hormone in vivo are likely to be indirect. It is concluded that regulation of Talpha1 alpha-tubulin by thyroid hormone is the result of multiple influences including effects on mRNA half life and indirect effects at the promoter level.
甲状腺激素（T3）对大脑发育至关重要，其大部分作用是在与核受体相互作用后在基因表达水平上发挥的。特别是，编码细胞骨架蛋白的基因受甲状腺状态的影响。甲状腺激素参与出生后生长过程中Tα1α-微管蛋白基因的正常下调。T3对Tα1微管蛋白表达的作用是复杂的，至少在两个水平上发挥作用。在培养细胞中，T3诱导Tα1 mRNA浓度短暂快速下降。当放线菌素D阻断转录时，这种效应增强，表明T3增加mRNA降解。在转基因动物中，T3以与内源基因相同的方式影响Tα1启动子控制下的β-半乳糖苷酶表达，支持通过Tα1启动子介导的效应。然而，Tα1启动子在转染细胞中不受T3调节，因此，激素在体内的作用可能是间接的。结论是，甲状腺激素对Tα1α-微管蛋白的调节是多种影响的结果，包括对mRNA半衰期的影响和在启动子水平的间接影响。
