Isometric force and endurance in soleus muscle of thyroid hormone receptor-α1- or -β-deficient mice

2000 ◽  
Vol 278 (3) ◽  
pp. R598-R603 ◽  
Author(s):  
Catarina Johansson ◽  
Jan Lännergren ◽  
Per-Kristian Lunde ◽  
Björn Vennström ◽  
Peter Thorén ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Isometric Force ◽  
Relaxation Times ◽  
Wild Type ◽  
Skeletal Muscle Function ◽  
Contraction And Relaxation ◽  
Deficient Mice

The specific role of each subtype of thyroid hormone receptor (TR) on skeletal muscle function is unclear. We have therefore studied kinetics of isometric twitches and tetani as well as fatigue resistance in isolated soleus muscles of R-α1- or -β-deficient mice. The results show 20–40% longer contraction and relaxation times of twitches and tetani in soleus muscles from TR-α1-deficient mice compared with their wild-type controls. TR-β-deficient mice, which have high thyroid hormone levels, were less fatigue resistant than their wild-type controls, but contraction and relaxation times were not different. Western blot analyses showed a reduced concentration of the fast-type sarcoplasmic reticulum Ca2+-ATPase (SERCa1) in TR-α1-deficient mice, but no changes were observed in TR-β-deficient mice compared with their respective controls. We conclude that in skeletal muscle, both TR-α1 and TR-β are required to get a normal thyroid hormone response.

scholarly journals Thyroid Hormone Receptor α Plays an Essential Role in Male Skeletal Muscle Myoblast Proliferation, Differentiation, and Response to Injury

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 4-15 ◽  
Author(s):  
Anna Milanesi ◽  
Jang-Won Lee ◽  
Nam-Ho Kim ◽  
Yan-Yun Liu ◽  
An Yang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Essential Role ◽  
Mutant Mouse ◽  
Thyroid Hormone Receptor ◽  
Myogenic Differentiation ◽  
Myoblast Differentiation ◽  
Primary Myoblasts ◽  
Myoblast Proliferation

Abstract Thyroid hormone plays an essential role in myogenesis, the process required for skeletal muscle development and repair, although the mechanisms have not been established. Skeletal muscle develops from the fusion of precursor myoblasts into myofibers. We have used the C2C12 skeletal muscle myoblast cell line, primary myoblasts, and mouse models of resistance to thyroid hormone (RTH) α and β, to determine the role of thyroid hormone in the regulation of myoblast differentiation. T3, which activates thyroid hormone receptor (TR) α and β, increased myoblast differentiation whereas GC1, a selective TRβ agonist, was minimally effective. Genetic approaches confirmed that TRα plays an important role in normal myoblast proliferation and differentiation and acts through the Wnt/β-catenin signaling pathway. Myoblasts with TRα knockdown, or derived from RTH-TRα PV (a frame-shift mutation) mice, displayed reduced proliferation and myogenic differentiation. Moreover, skeletal muscle from the TRα1PV mutant mouse had impaired in vivo regeneration after injury. RTH-TRβ PV mutant mouse model skeletal muscle and derived primary myoblasts did not have altered proliferation, myogenic differentiation, or response to injury when compared with control. In conclusion, TRα plays an essential role in myoblast homeostasis and provides a potential therapeutic target to enhance skeletal muscle regeneration.

scholarly journals Adaptations of the Autonomous Nervous System Controlling Heart Rate Are Impaired by a Mutant Thyroid Hormone Receptor-α1

Endocrinology ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2388-2395 ◽  
Author(s):  
Jens Mittag ◽  
Benjamin Davis ◽  
Milica Vujovic ◽  
Anders Arner ◽  
Björn Vennström
Keyword(s):  
Heart Rate ◽  
Nervous System ◽  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Cardiac Activity ◽  
Autonomic Control ◽  
Autonomous Nervous System ◽  
Wild Type ◽  
Brown Adipose

Thyroid hormone has profound direct effects on cardiac function, but the hormonal interactions with the autonomic control of heart rate are unclear. Because thyroid hormone receptor (TR)-α1 has been implicated in the autonomic control of brown adipose energy metabolism, it might also play an important role in the central autonomic control of heart rate. Thus, we aimed to analyze the role of TRα1 signaling in the autonomic control of heart rate using an implantable radio telemetry system. We identified that mice expressing the mutant TRα1R384C (TRα1+m mice) displayed a mild bradycardia, which becomes more pronounced during night activity or on stress and is accompanied by a reduced expression of nucleotide-gated potassium channel 2 mRNA in the heart. Pharmacological blockage with scopolamine and the β-adrenergic receptor antagonist timolol revealed that the autonomic control of cardiac activity was similar to that in wild-type mice at room temperature. However, at thermoneutrality, in which the regulation of heart rate switches from sympathetic to parasympathetic in wild-type mice, TRα1+m mice maintained sympathetic stimulation and failed to activate parasympathetic signaling. Our findings demonstrate a novel role for TRα1 in the adaptation of cardiac activity by the autonomic nervous system and suggest that human patients with a similar mutation in TRα1 might exhibit a deficit in cardiac adaptation to stress or physical activity and an increased sensitivity to β-blockers.

Evidence that decreased heart rate in thyroid hormone receptor-α1-deficient mice is an intrinsic defect

1998 ◽  
Vol 275 (2) ◽  
pp. R640-R646 ◽  
Author(s):  
Catarina Johansson ◽  
Björn Vennström ◽  
Peter Thorén
Keyword(s):  
Heart Rate ◽  
Thyroid Hormone ◽  
Body Temperature ◽  
Hormone Receptor ◽  
Adrenergic Receptor ◽  
Thyroid Hormone Receptor ◽  
Intrinsic Defect ◽  
Air Jet ◽  
Parallel Increase ◽  
Deficient Mice

Using a telemetry system with implantable transmitters, we recorded heart rate, electrocardiogram (ECG), body temperature, and locomotor activity continuously in awake, freely moving mice deficient in the thyroid hormone receptor-α1 (TRα1). We have previously reported that the TRα1-deficient mice have a 20% lower mean heart rate and a 0.5°C lower body temperature compared with wild-type control animals. In this study we found that when 3,5,3′-triiodothyronine (T3) was given once a day, there was a parallel increase in heart rate (occurring 1 day later in the TRα1-deficient mice than in controls) and body temperature. Analysis of single-lead ECG revealed a prolonged QRS and Q-Tend time in the TRα1-deficient mice, which was shortened after T3 treatment. Monophasic action potential durations, measured in hearts from anesthetized mice at 90% of repolarization, were significantly prolonged in TRα1-deficient mice. Air-jet stress and a single injection of an anticholinergic agent induced a parallel increase, and a β-adrenergic receptor blocker induced a decrease in heart rate in both groups. There was no difference in β-adrenergic receptor density. The results indicate that the TRα1-deficient mice have a specific defect in intrinsic heart rate regulation.

Skeletal muscle expression of p43, a truncated thyroid hormone receptor α, affects lipid composition and metabolism

2018 ◽  
Vol 50 (1) ◽  
pp. 71-79
Author(s):  
François Casas ◽  
Gilles Fouret ◽  
Jérome Lecomte ◽  
Fabienne Cortade ◽  
Laurence Pessemesse ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Hormone ◽  
Lipid Composition ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Thyroid Hormone Receptor Α

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

Quantitative Analysis of DNA Binding Affinity and Dimerization Properties of Wild-Type and Mutant Thyroid Hormone Receptor β1

Thyroid ◽  
2000 ◽  
Vol 10 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Teiji Takeda ◽  
Takeshi Nagasawa ◽  
Takahide Miyamoto ◽  
Kesami Minemura ◽  
Kiyoshi Hashizume ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Thyroid Hormone ◽  
Dna Binding ◽  
Binding Affinity ◽  
Hormone Receptor ◽  
Thyroid Hormone Receptor ◽  
Wild Type ◽  
Dna Binding Affinity

Aberrant expression of myosin isoforms in skeletal muscles from mice lacking the rev-erbAα orphan receptor gene

2005 ◽  
Vol 288 (2) ◽  
pp. R482-R490 ◽  
Author(s):  
P. Pircher ◽  
P. Chomez ◽  
F. Yu ◽  
B. Vennström ◽  
L. Larsson
Keyword(s):  
Thyroid Hormone ◽  
Hormone Receptor ◽  
Skeletal Muscles ◽  
Extensor Digitorum Longus ◽  
Thyroid Hormone Receptor ◽  
Extensor Digitorum ◽  
Type I ◽  
Wild Type ◽  
Slow Twitch ◽  
Isoform Expression

The rev-erbAα orphan protein belongs to the steroid nuclear receptor superfamily. No ligand has been identified for this protein, and little is known of its function in development or physiology. In this study, we focus on 1) the distribution of the rev-erbAα protein in adult fast- and slow-twitch skeletal muscles and muscle fibers and 2) how the rev-erbAα protein influences myosin heavy chain (MyHC) isoform expression in mice heterozygous (+/−) and homozygous (−/−) for a rev-erbAα protein null allele. In the fast-twitch extensor digitorum longus muscle, rev-erbAα protein expression was linked to muscle fiber type; however, MyHC isoform expression did not differ between wild-type, +/−, or −/− mice. In the slow-twitch soleus muscle, the link between rev-erbAα protein and MyHC isoform expression was more complex than in the extensor digitorum longus. Here, a significantly higher relative amount of the β/slow (type I) MyHC isoform was observed in both rev-erbAα −/− and +/− mice vs. that shown in wild-type controls. A role for the ratio of thyroid hormone receptor proteins α1 to α2 in modulating MyHC isoform expression can be ruled out because no differences were seen in MyHC isoform expression between thyroid hormone receptor α2-deficient mice (heterozygous and homozygous) and wild-type mice. Therefore, our data are compatible with the rev-erbAα protein playing an important role in the regulation of skeletal muscle MyHC isoform expression.

Sign in / Sign up

Export Citation Format

Share Document