Vallejo Carmen G, Seguido Ana M, Testillano Pilar S, Risueño María-Carmen
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier, 4, 28029 Madrid, Spain.
Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E87-94. doi: 10.1152/ajpendo.00436.2004. Epub 2005 Feb 15.
Microtubules are made from polymers of alpha/beta dimers. We have observed in rat liver that, on the first day after birth, alpha-subunit is relatively high and beta-subunit low with respect to adult values. In the hypothyroid neonate, both subunits were found to be low, therefore indicating that thyroid hormone (TH) regulates these developmental changes. TH was also found to activate tubulin expression in adult liver, especially beta-subunit. To investigate the role of TH receptors (TRs) in tubulin expression, we analyzed mice lacking TRalpha or TRbeta compared with the wild type in both normal and TH-deprived adult animals. The results suggest that, in vivo, beta-tubulin protein expression in the liver is primarily under TRbeta positive control. In euthyroid mice lacking TRbeta, beta-tubulin expression was low. However, in the corresponding hypothyroid animals, it was found increased, therefore suggesting that the unliganded TRalpha might also upregulate beta-tubulin expression. Accordingly, TH administration to hypothyroid TRbeta-deprived mice reduced their high beta-tubulin expression. In parallel, the relatively high messenger level observed with these hypothyroid animals was reduced to the euthyroid level after T(3) treatment. The microtubular network of the mutant livers appeared, by immunofluorescence confocal microscopy, generally disorganized and drastically reduced in beta-tubulin in mice lacking TRbeta. In conclusion, our results indicate that beta-tubulin is critically controlled by TRbeta in the liver and that both TRs are probably needed to maintain the microtubular network organization of the liver.
微管由α/β二聚体聚合物构成。我们在大鼠肝脏中观察到，出生后第一天，相对于成年大鼠的值，α亚基含量相对较高，β亚基含量较低。在甲状腺功能减退的新生儿中，发现两个亚基的含量都较低，因此表明甲状腺激素（TH）调节这些发育变化。还发现TH可激活成年肝脏中的微管蛋白表达，尤其是β亚基。为了研究TH受体（TRs）在微管蛋白表达中的作用，我们分析了在正常和缺乏TH的成年动物中，与野生型相比缺乏TRα或TRβ的小鼠。结果表明，在体内，肝脏中β-微管蛋白的表达主要受TRβ的正向调控。在缺乏TRβ的甲状腺功能正常的小鼠中，β-微管蛋白的表达较低。然而，在相应的甲状腺功能减退的动物中，发现其表达增加，因此表明未结合配体的TRα也可能上调β-微管蛋白的表达。相应地，对缺乏TRβ的甲状腺功能减退小鼠给予TH可降低其较高的β-微管蛋白表达。同时，在这些甲状腺功能减退的动物中观察到的相对较高的信使水平在T3治疗后降至甲状腺功能正常的水平。通过免疫荧光共聚焦显微镜观察，在缺乏TRβ的小鼠中，突变肝脏的微管网络通常显得杂乱无章，且β-微管蛋白大幅减少。总之，我们的结果表明，β-微管蛋白在肝脏中受TRβ的严格控制，并且可能需要两个TRs来维持肝脏微管网络的组织。
