Thyroid Hormone-Regulated Mouse Cerebral Cortex Genes Are Differentially Dependent on the Source of the Hormone: A Study in Monocarboxylate Transporter-8- and Deiodinase-2-Deficient Mice
| Autor: | Caterina Di Cosmo, Diego Diez, Juan Bernal, Samuel Refetoff, Ainhoa Ceballos, Beatriz Morte, Carmen Grijota-Martínez, Alexandra M. Dumitrescu, Valerie Anne Galton |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Monocarboxylic Acid Transporters Thyroid Hormones medicine.medical_specialty Deiodinase DIO2 Iodide Peroxidase Article Type-2 iodothyronine deiodinase Mice Endocrinology Antithyroid Agents Hypothyroidism Pregnancy Internal medicine Gene expression medicine Animals Blood-brain-barrier Oligonucleotide Array Sequence Analysis Cerebral Cortex Mice Knockout Regulation of gene expression Methimazole Triiodothyronine Symporters biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Thyroid Gene Expression Regulation Developmental Membrane Transport Proteins Rat-brain Mice Inbred C57BL Gene expression profiling Thyroxine medicine.anatomical_structure Animals Newborn biology.protein Female Hormone |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2009-0944 |
| Popis: | 7 páginas, 4 figuras.-- et al. Thyroid hormones influence brain development through the control of gene expression. The concentration of the active hormone T-3 in the brain depends on T-3 transport through the blood-brain barrier, mediated in part by the monocarboxylate transporter 8 (Mct8/MCT8) and the activity of type 2 deiodinase (D2) generating T-3 from T-4. The relative roles of each of these pathways in the regulation of brain gene expression is not known. To shed light on this question, we analyzed thyroid hormone-dependent gene expression in the cerebral cortex of mice with inactivated Mct8 (Slc16a2) and Dio2 genes, alone or in combination. We used 34 target genes identified to be controlled by thyroidhormone in microarray comparisons of cerebral cortex from wild-type control and hypothyroid mice on postnatal d 21. Inactivation of the Mct8 gene (Mct8KO) was without effect on the expression of 31 of these genes. Normal gene expression in the absence of the transporter was mostly due to D2 activity because the combined disruption of Mct8 and Dio2 led to similar effects as hypothyroidism on the expression of 24 genes. Dio2 disruption alone did not affect the expression of positively regulated genes, but, as in hypothyroidism, it increased that of negatively regulated genes. We conclude that gene expression in the Mct8KO cerebral cortex is compensated in part by D2-dependent mechanisms. Intriguingly, positive or negative regulation of genes by thyroid hormone is sensitive to the source of T3 because Dio2 inactivation selectively affects the expression of negatively regulated genes. This work was supported by the Center for Biomedical Research on Rare Diseases; Grants SAF2008-01168 and SAF2008-00429E from the Ministry of Science and Innovation, Spain; the European Union Integrated Project CRESCENDO (LSHM-CT-2005-018652) Grants DK15070, DK07011, and DK20595 from the National Institutes of Health; and the Sherman family. A.C. is the holder of a predoctoral fellowship from the Ministry of Science and Innovation of Spain. |
| Databáze: | OpenAIRE |
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