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

Carmen Grijota-Martínez, Eric Samarut, Thomas (Tom) Scanlan, Beatriz Morte, Juan Bernal

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1136-1142
Number of pages7
JournalEndocrinology
Volume152
Issue number3
DOIs
StatePublished - Mar 2011

Fingerprint

Thyroid Hormone Receptors
Hormones
Liver
Brain
Thyroid Hormones
Organ Specificity
Genes
Larva
Pharmacology

ASJC Scopus subject areas

  • Endocrinology

Cite this

In vivo activity of the thyroid hormone receptor β- and α-selective agonists GC-24 and CO23 on rat liver, heart, and brain. / Grijota-Martínez, Carmen; Samarut, Eric; Scanlan, Thomas (Tom); Morte, Beatriz; Bernal, Juan.

In: Endocrinology, Vol. 152, No. 3, 03.2011, p. 1136-1142.

Research output: Contribution to journalArticle

Grijota-Martínez, Carmen ; Samarut, Eric ; Scanlan, Thomas (Tom) ; Morte, Beatriz ; Bernal, Juan. / In vivo activity of the thyroid hormone receptor β- and α-selective agonists GC-24 and CO23 on rat liver, heart, and brain. In: Endocrinology. 2011 ; Vol. 152, No. 3. pp. 1136-1142.
@article{e6d25506b56b4bf4b51dd3fad98a0038,
title = "In vivo activity of the thyroid hormone receptor β- and α-selective agonists GC-24 and CO23 on rat liver, heart, and brain",
abstract = "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.",
author = "Carmen Grijota-Mart{\'i}nez and Eric Samarut and Scanlan, {Thomas (Tom)} and Beatriz Morte and Juan Bernal",
year = "2011",
month = "3",
doi = "10.1210/en.2010-0813",
language = "English (US)",
volume = "152",
pages = "1136--1142",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "3",

}

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 (Tom)

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.

UR - http://www.scopus.com/inward/record.url?scp=79951904578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951904578&partnerID=8YFLogxK

U2 - 10.1210/en.2010-0813

DO - 10.1210/en.2010-0813

M3 - Article

C2 - 21239431

AN - SCOPUS:79951904578

VL - 152

SP - 1136

EP - 1142

JO - Endocrinology

JF - Endocrinology

SN - 0013-7227

IS - 3

ER -