TY - JOUR
T1 - In vivo activity of the thyroid hormone receptor β- and α-selective agonists GC-24 and CO23 on rat liver, heart, and brain
AU - Grijota-Martínez, Carmen
AU - Samarut, Eric
AU - Scanlan, Thomas S.
AU - Morte, Beatriz
AU - Bernal, Juan
PY - 2011/3
Y1 - 2011/3
N2 - 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,westudied the in vivo activity in developing rats of two thyroid hormone agonists, the TRβ-selective GC-24 and the TRβ-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 TRβ and lacked activity on the brain. On the other hand, CO23 was active in liver, heart, and brain on genes regulated by either TRα or TRβ. This compound, previously shown to be TRα-selective in tadpoles, displayed no selectivity in the rat in vivo.
AB - 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,westudied the in vivo activity in developing rats of two thyroid hormone agonists, the TRβ-selective GC-24 and the TRβ-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 TRβ and lacked activity on the brain. On the other hand, CO23 was active in liver, heart, and brain on genes regulated by either TRα or TRβ. This compound, previously shown to be TRα-selective in tadpoles, displayed no selectivity in the rat in vivo.
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U2 - 10.1210/en.2010-0813
DO - 10.1210/en.2010-0813
M3 - Article
C2 - 21239431
AN - SCOPUS:79951904578
SN - 0013-7227
VL - 152
SP - 1136
EP - 1142
JO - Endocrinology
JF - Endocrinology
IS - 3
ER -