Thyroid hormone regulates tubulin expression in mammalian liver. Effects of deleting thyroid hormone receptor-α or -β

Abstract

Microtubules are made from polymers of α/β dimers. We have observed in rat liver that, on the first day after birth, α-subunit is relatively high and β-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 β-subunit. To investigate the role of TH receptors (TRs) in tubulin expression, we analyzed mice lacking TRα or TRβ compared with the wild type in both normal and TH-deprived adult animals. The results suggest that, in vivo, β-tubulin protein expression in the liver is primarily under TRβ positive control. In euthyroid mice lacking TRβ, β-tubulin expression was low. However, in the corresponding hypothyroid animals, it was found increased, therefore suggesting that the unliganded TRα might also upregulate β-tubulin expression. Accordingly, TH administration to hypothyroid TRβ-deprived mice reduced their high β-tubulin expression. In parallel, the relatively high messenger level observed with these hypothyroid animals was reduced to the euthyroid level after T3treatment. The microtubular network of the mutant livers appeared, by immunofluorescence confocal microscopy, generally disorganized and drastically reduced in β-tubulin in mice lacking TRβ. In conclusion, our results indicate that β-tubulin is critically controlled by TRβ in the liver and that both TRs are probably needed to maintain the microtubular network organization of the liver.