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Publication : Role of thyroid hormone receptor subtypes α and β on gene expression in the cerebral cortex and striatum of postnatal mice.

First Author  Gil-Ibañez P Year  2013
Journal  Endocrinology Volume  154
Issue  5 Pages  1940-7
PubMed ID  23493375 Mgi Jnum  J:197931
Mgi Id  MGI:5494912 Doi  10.1210/en.2012-2189
Citation  Gil-Ibanez P, et al. (2013) Role of thyroid hormone receptor subtypes alpha and beta on gene expression in the cerebral cortex and striatum of postnatal mice. Endocrinology 154(5):1940-7
abstractText  The effects of thyroid hormones (THs) on brain development and function are largely mediated by the control of gene expression. This is achieved by the binding of the genomically active T3 to transcriptionally active nuclear TH receptors (TRs). T3 and the TRs can either induce or repress transcription. In hypothyroidism, the reduction of T3 lowers the expression of a set of genes, the positively regulated genes, and increases the expression of negatively regulated genes. Two mechanisms may account for the effect of hypothyroidism on genes regulated directly by T3: first, the loss of T3 signaling and TR transactivation, and second, an intrinsic activity of the unliganded TRs directly responsible for repression of positive genes and enhancement of negative genes. To analyze the contribution of the TR subtypes alpha and beta, we have measured by RT-PCR the expression of a set of positive and negative genes in the cerebral cortex and the striatum of TR-knockout male and female mice. The results indicate that TRalpha1 exerts a predominant but not exclusive role in the regulation of positive and negative genes. However, a fraction of the genes analyzed are not or only mildly affected by the total absence of TRs. Furthermore, hypothyroidism has a mild effect on these genes in the absence of TRalpha1, in agreement with a role of unliganded TRalpha1 in the effects of hypothyroidism.
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