Thyroid hormone receptor-β-selective agonist GC-24 spares skeletal muscle type I to II fiber shift

2005 ◽  
Vol 321 (2) ◽  
pp. 233-241 ◽  
Author(s):  
Elen H. Miyabara ◽  
Marcelo S. Aoki ◽  
Antonio G. Soares ◽  
Rodrigo M. Saltao ◽  
Cassio M. Vilicev ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Type I ◽  
Muscle Type ◽  
Selective Agonist ◽  
Thyroid Hormone Receptor Β

scholarly journals Thyroid hormone receptor-β agonists prevent hepatic steatosis in fat-fed rats but impair insulin sensitivity via discrete pathways

2013 ◽  
Vol 305 (1) ◽  
pp. E89-E100 ◽  
Author(s):  
Daniel F. Vatner ◽  
Dirk Weismann ◽  
Sara A. Beddow ◽  
Naoki Kumashiro ◽  
Derek M. Erion ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Thyroid Hormone ◽  
Hepatic Steatosis ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hepatic Insulin Resistance ◽  
Lipid Lowering ◽  
Hepatic Insulin Sensitivity ◽  
Thyroid Hormone Receptor Β

Liver-specific thyroid hormone receptor-β (TRβ)-specific agonists are potent lipid-lowering drugs that also hold promise for treating nonalcoholic fatty liver disease and hepatic insulin resistance. We investigated the effect of two TRβ agonists (GC-1 and KB-2115) in high-fat-fed male Sprague-Dawley rats treated for 10 days. GC-1 treatment reduced hepatic triglyceride content by 75%, but the rats developed fasting hyperglycemia and hyperinsulinemia, attributable to increased endogenous glucose production (EGP) and diminished hepatic insulin sensitivity. GC-1 also increased white adipose tissue lipolysis; the resulting increase in glycerol flux may have contributed to the increase in EGP. KB-2115, a more TRβ- and liver-specific thyromimetic, also prevented hepatic steatosis but did not induce fasting hyperglycemia, increase basal EGP rate, or diminish hepatic insulin sensitivity. Surprisingly, insulin-stimulated peripheral glucose disposal was diminished because of a decrease in insulin-stimulated skeletal muscle glucose uptake. Skeletal muscle insulin signaling was unaffected. Instead, KB-2115 treatment was associated with a decrease in GLUT4 protein content. Thus, although both GC-1 and KB-2115 potently treat hepatic steatosis in fat-fed rats, they each worsen insulin action via specific and discrete mechanisms. The development of future TRβ agonists must consider the potential adverse effects on insulin sensitivity.

scholarly journals The Thyroid Hormone Receptor-β-Selective Agonist GC-1 Differentially Affects Plasma Lipids and Cardiac Activity1

Endocrinology ◽  
2000 ◽  
Vol 141 (9) ◽  
pp. 3057-3064 ◽  
Author(s):  
Susanne U. Trost ◽  
Eric Swanson ◽  
Bernd Gloss ◽  
David B. Wang-Iverson ◽  
Hongjiang Zhang ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Plasma Lipids ◽  
Thyroid Hormone Receptor ◽  
Selective Agonist ◽  
Thyroid Hormone Receptor Β

scholarly journals The thyroid hormone receptor β-selective agonist GC-1 does not affect tolerance to exercise in hypothyroid rats

2015 ◽  
Vol 59 (2) ◽  
pp. 141-147 ◽  
Author(s):  
Alexandre Gonçalves ◽  
Chineyder Corrêa Tolentino ◽  
Fernanda Rodrigues de Souza ◽  
Juliana Carla da Costa Huss ◽  
Karolinne de Lourdes Zinato ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Selective Agonist ◽  
Thyroid Hormone Receptor Β

scholarly journals Thyroid hormone receptor β mutations in the ‘hot-spot region’ are rare events in thyroid carcinomas

2007 ◽  
Vol 192 (1) ◽  
pp. 83-86 ◽  
Author(s):  
Ana Sofia Rocha ◽  
Ricardo Marques ◽  
Inês Bento ◽  
Ricardo Soares ◽  
João Magalhães ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Hormone ◽  
Transgenic Mice ◽  
Cell Lines ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Hot Spot ◽  
Direct Sequencing ◽  
Human Thyroid ◽  
Thyroid Hormone Receptor Β

Thyroid cancer constitutes the most frequent endocrine neoplasia. Targeted expression of rearranged during transfection (RET)/papillary thyroid carcinoma (PTC) and V600E V-raf murine sarcoma viral oncogene homolog B1 (BRAF) to the thyroid glands of transgenic mice results in tumours similar to those of human PTC, providing evidence for the involvement of these oncogenes in PTC. Kato et al. developed a mouse model that mimics the full spectrum of the human follicular form of thyroid cancer (FTC). FTC rapidly develops in these mice through introduction of the thyroid hormone receptor β (THRB)PV mutant on the background of the inactivated THRB wt locus. Our aim was to verify if, in the context of human follicular thyroid carcinogenesis, THRB acted as a tumour suppressor gene. We screened for mutations of the THRB gene in the hot-spot region, spanning exons 7–10, in 51 thyroid tumours and six thyroid cancer cell lines by PCR and direct sequencing. We did not find mutations in any of the tumours or cell lines analysed. Our findings suggest that, in contrast to the findings on the THRB-mutant transgenic mice, THRB gene mutations are not a relevant mechanism for human thyroid carcinogenesis.

A Novel Point Mutation of Thyroid Hormone Receptor β Gene in a Family with Resistance to Thyroid Hormone

Thyroid ◽  
1997 ◽  
Vol 7 (5) ◽  
pp. 771-773 ◽  
Author(s):  
TOMOHISA NAGASHIMA ◽  
HIDEKI YAGI ◽  
KANJI NAGASHIMA ◽  
AKIHIRO SAKURAI ◽  
KAZUMICHI ONIGATA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Point Mutation ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Resistance To Thyroid Hormone ◽  
Thyroid Hormone Receptor Β

scholarly journals Oncogenic mutations of thyroid hormone receptor β

Oncotarget ◽  
2015 ◽  
Vol 6 (10) ◽  
pp. 8115-8131 ◽  
Author(s):  
Jeong Won Park ◽  
Li Zhao ◽  
Mark Willingham ◽  
Sheue-yann Cheng
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Oncogenic Mutations ◽  
Thyroid Hormone Receptor Β

scholarly journals In Vivo Activity of the Thyroid Hormone Receptor β- and α-Selective Agonists GC-24 and CO23 on Rat Liver, Heart, and Brain

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 1136-1142 ◽  
Author(s):  
Carmen Grijota-Martínez ◽  
Eric Samarut ◽  
Thomas S. Scanlan ◽  
Beatriz Morte ◽  
Juan Bernal
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Target Genes ◽  
Thyroid Hormone Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Genetic Modifications ◽  
Hormone Analogs ◽  
Thyroid Hormone Receptor Β

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 TRβ-selective GC-24 and the TRα-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.

scholarly journals Thyroid Hormone-mediated Enhancement of Heterodimer Formation between Thyroid Hormone Receptor β and Retinoid X Receptor

1997 ◽  
Vol 272 (20) ◽  
pp. 13060-13065 ◽  
Author(s):  
Trevor N. Collingwood ◽  
Alison Butler ◽  
Yukiko Tone ◽  
Rory J. Clifton-Bligh ◽  
Malcolm G. Parker ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Retinoid X Receptor ◽  
Thyroid Hormone Receptor Β
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