Is the Intrinsic Genomic Activity of Thyroxine Relevant In Vivo? Effects on Gene Expression in Primary Cerebrocortical and Neuroblastoma Cells
| Autor: | Juan Bernal, María Jesús Obregón, Beatriz Morte, Pilar Gil-Ibáñez, Mónica M. Belinchón |
|---|---|
| Přispěvatelé: | Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red Enfermedades Raras (España), Ministerio de Economía y Competitividad (España), European Commission |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Cell type Endocrinology Diabetes and Metabolism N2a cells Rgs4 DIO2 030209 endocrinology & metabolism Nerve Tissue Proteins Biology Iodide Peroxidase Cell Line Avian Proteins 03 medical and health sciences Mice Neuroblastoma 0302 clinical medicine Endocrinology In vivo Gene expression medicine Animals Gene Cells Cultured Cerebral Cortex Mice Knockout Neurons Thyroxine activity Triiodothyronine Thyroid hormone receptor Thyroid Gene Expression Regulation Developmental Cerebrocortical cells Embryo Mammalian Molecular biology Recombinant Proteins Neoplasm Proteins Gene Expression Regulation Neoplastic Thyroxine 030104 developmental biology medicine.anatomical_structure Astrocytes Zcchc12 Chickens Thyroid Hormone Receptors alpha |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1557-9077 |
| Popis: | [Background]: The possibility that the intrinsic genomic activity of thyroxine (T4) is of physiological relevance has been frequently hypothesized. It might explain gene expression patterns in the brain found in type 2-deiodinase (Dio2)-deficient mice. These mice display normal expression of most thyroid hormone–dependent genes, despite decreased brain triiodothyronine (T3). [Methods]: The relative effects of T4 and T3 on gene expression were analyzed in mouse neuro-2a (N2a) cells stably expressing the thyroid hormone receptor α1, and in primary mouse cerebrocortical cells enriched in astrocytes or in neurons. Cortical cells were derived from Dio2-deficient mice to prevent conversion of T4 to T3. T4 and T3 were measured in the media at the beginning and end of incubation, and T4 and T3 antibodies were used to block T4 and T3 action. [Results]: In all cell types, T4 had intrinsic genomic activity. In N2a cells, T4 activity was higher on negative regulation (1/5th of T3 activity) than on positive regulation (1/40th of T3 activity). T4 activity on positive regulation was dependent on the cell context, and was higher in primary cells than in N2a cells. [Conclusion]: T4 has intrinsic genomic activity. Positive regulation depends on the cell context, and primary cells appear much more sensitive than neuroblastoma cells. In all cells, negative regulation is more sensitive to T4 than positive regulation. These properties may explain the mostly normal gene expression in the brain of Dio2-deficient mice. This work was supported by the Center for Biomedical Research on Rare Diseases (Ciberer) under the frame of E-Rare-2 (project acronym THYRONERVE), the ERA-Net for Research on Rare Diseases; grant SAF2014-54919R from Plan Estatal de Investigación Científica, Técnica y de Innovación, Ministerio de Economía y Competititividad, and FEDER funds. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|