In vivo activity of the thyroid hormone receptor β- and α-selective agonists GC-24 and CO23 on rat liver, heart, and brain
Thyroid hormone analogs with selective actions through specific thyroid hormone receptor (TR) subtypes are of great interest. They might offer the possibility of mimicking physiological actions of thyroid hormone with receptor subtype or tissue specificity with therapeutic aims. They are also pharma...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2011 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/40190 |
| Acceso en línea: | http://hdl.handle.net/10261/40190 |
| Access Level: | acceso abierto |
| Palabra clave: | Ligand selectivity Cholesterol Genes Triiodothyronine Deiodinase |
| Sumario: | Thyroid hormone analogs with selective actions through specific thyroid hormone receptor (TR) subtypes are of great interest. They might offer the possibility of mimicking physiological actions of thyroid hormone with receptor subtype or tissue specificity with therapeutic aims. They are also pharmacological tools to dissect biochemical pathways mediated by specific receptor subtypes, in a complementary way to mouse genetic modifications. In this work, we studied the in vivo activity in developing rats of two thyroid hormone agonists, the TR beta-selective GC-24 and the TR beta-selective CO23. Our principal goal was to check whether these compounds were active in the rat brain. Analog activity was assessed by measuring the expression of thyroid hormone target genes in liver, heart, and brain, after administration to hypothyroid rats. GC-24 was very selective for TR beta and lacked activity on the brain. On the other hand, CO23 was active in liver, heart, and brain on genes regulated by either TR alpha or TR beta. This compound, previously shown to be TR alpha-selective in tadpoles, displayed no selectivity in the rat in vivo. |
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