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Evidence for a role of unliganded thyroid hormone receptors on cerebrocortical neurons in primary culture

AutorGil-Ibáñez, Pilar ; Morte, Beatriz ; Bernal, Juan
Fecha de publicación2013
CitaciónETA 2013
Resumen[Objectives]: Thyroid hormone receptors (TRs) have a dual action: transcriptional repressors in the absence of T3, and transcriptional activators in its presence on positively regulated genes, and the opposite on negatively regulated genes. The relevance of this phenomenon has been demonstrated during amphibian premetamorphosis, but its significance during mammalian brain development is unclear. Our objective was to study whether unliganded TRs regulate the expression of T3-regulated genes in primary neurons. [Methods]: Primary neurons were isolated from cerebral cortex of wild type (WT), and TRα1/TRβ KO mice. Gene expression was measured by Taqman PCR in the presence or absence of 10 nM T3 in the cultures. As targets we used 3 genes identified as thyroid hormone dependent in vivo in the mouse brain: Aldh1a1 as a positively regulated gene, Calb1 as a negatively regulated gene, and the sensitive T3 target gene Hr as control. [Results]: In WT neurons Hr was induced 7-fold after addition of T3. The absence of all forms of TRs resulted in Hr expression similar to that of WT neurons without T3. No evidence for a dual role of TRs was obtained for Hr. In WT neurons Aldh1a1 was induced 2-fold by T3. However in the absence of TRs Aldh1a1 expression was 10-fold higher than in WT neurons. The results suggest a strong unliganded TRs repressor activity on Aldh1a1. Calb1 was repressed 2-fold by T3 in the WT neurons. In the absence of TRs Calb1 expression was 10-fold lower than in the WT neurons, suggesting a strong unliganded TRs induction on Calb1. [Conclusions]: We demonstrate that in primary neurons TRs have strong unliganded activity on gene expression. The results open new perspectives on the role of TRs in early development.
DescripciónResumen del trabajo presentado al 37th Annual Meeting of the European Thyroid Association, celebrado en Leiden (Holanda) del 7 al 11 de septiembre de 2013.
URIhttp://hdl.handle.net/10261/125409
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