Thyroid hormone regulates tubulin expression in mammalian liver. Effects of deleting thyroid hormone receptor-alpha or -beta.
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.
Vallejo
Carmen G
CG
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Arturo Duperier, 4, 28029 Madrid, Spain. cvallejo@iib.uam.es
Seguido
Ana M
AM
Testillano
Pilar S
PS
Risueño
María-Carmen
MC
D000818:Animals; D000831:Animals, Newborn; D007037:Hypothyroidism / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar; D011988:Receptors, Thyroid Hormone / Q000172:deficiency*; D037021:Thyroid Hormone Receptors alpha / Q000172:deficiency*; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism* / Q000648:ultrastructure
D011988:Receptors, Thyroid Hormone; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D014404:Tubulin