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This Article Full Text Full Text (PDF) All Versions of this Article: 289/1/E87    most recent 00436.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Vallejo, C. G. Articles by Risueño, M.-C. Search for Related Content PubMed PubMed Citation Articles by Vallejo, C. G. Articles by Risueño, M.-C.

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

¹Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid; and ²Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas, Madrid, Spain

Submitted 14 September 2004 ; accepted in final form 3 February 2005

Microtubules are made from polymers of / dimers. We have observed in rat liver that, on the first day after birth, -subunit is relatively high and -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 -subunit. To investigate the role of TH receptors (TRs) in tubulin expression, we analyzed mice lacking TR or TR compared with the wild type in both normal and TH-deprived adult animals. The results suggest that, in vivo, -tubulin protein expression in the liver is primarily under TR positive control. In euthyroid mice lacking TR, -tubulin expression was low. However, in the corresponding hypothyroid animals, it was found increased, therefore suggesting that the unliganded TR might also upregulate -tubulin expression. Accordingly, TH administration to hypothyroid TR-deprived mice reduced their high -tubulin expression. In parallel, the relatively high messenger level observed with these hypothyroid animals was reduced to the euthyroid level after T₃ treatment. The microtubular network of the mutant livers appeared, by immunofluorescence confocal microscopy, generally disorganized and drastically reduced in -tubulin in mice lacking TR. In conclusion, our results indicate that -tubulin is critically controlled by TR in the liver and that both TRs are probably needed to maintain the microtubular network organization of the liver.

rat; knockout mice; Northern analysis; Western analysis; histological examination; immunofluorescence confocal microscopy