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Title

In vivo activity of the thyroid hormone receptor β- and α-selective agonists GC-24 and CO23 on rat liver, heart, and brain

AuthorsGrijota Martínez, María del Carmen; Samarut, Eric; Scanlan, Thomas S.; Morte, Beatriz ; Bernal, Juan
KeywordsLigand selectivity
Cholesterol
Genes
Triiodothyronine
Deiodinase
Issue Date1-Mar-2011
PublisherEndocrine Society
CitationEndocrinology 152(3): 1136-1142 (2011)
AbstractThyroid 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.
Publisher version (URL)http://doi.dx.org/10.1210/en.2010-0813
URIhttp://hdl.handle.net/10261/40190
DOI10.1210/en.2010-0813
ISSN0013-7227
E-ISSN1945-7170
Appears in Collections:(IIBM) Artículos
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