Related Experiment Videos
Isometric force and endurance in soleus muscle of thyroid hormone receptor-alpha(1)- or -beta-deficient mice
C Johansson1, J Lännergren, P K Lunde
1Department of Physiology and Pharmacology, Karolinska Institute, S-171 77 Stockholm, Sweden. catarina.johansson@fyfa.ki.se
Abstract:
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-alpha(1)- or -beta-deficient mice. The results show 20-40% longer contraction and relaxation times of twitches and tetani in soleus muscles from TR-alpha(1)-deficient mice compared with their wild-type controls. TR-beta-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 Ca(2+)-ATPase (SERCa1) in TR-alpha(1)-deficient mice, but no changes were observed in TR-beta-deficient mice compared with their respective controls. We conclude that in skeletal muscle, both TR-alpha(1) and TR-beta are required to get a normal thyroid hormone response.
Insights
Thyroid hormone receptors (TR) are crucial for skeletal muscle function. TR-alpha(1) deficiency slows muscle contraction, while TR-beta deficiency reduces fatigue resistance, indicating both receptor subtypes are vital.
Area of Science:
- Endocrinology
- Muscle Physiology
- Molecular Biology
Background:
- Thyroid hormones regulate metabolism and development.
- The distinct roles of thyroid hormone receptor (TR) subtypes, TR-alpha(1) and TR-beta, in skeletal muscle function remain incompletely understood.
- Skeletal muscle performance is sensitive to thyroid hormone status.
Purpose of the Study:
- To investigate the specific roles of TR-alpha(1) and TR-beta in regulating skeletal muscle contractile properties and fatigue resistance.
- To elucidate the molecular mechanisms underlying TR subtype-specific effects on muscle function.
Main Methods:
- Studied isometric twitch and tetanic contractions in isolated soleus muscles from TR-alpha(1)-deficient, TR-beta-deficient, and wild-type mice.
- Assessed fatigue resistance of soleus muscles.
- Analyzed the expression of key proteins, including sarcoplasmic reticulum Ca(2+)-ATPase (SERCa1), using Western blot.
Main Results:
- TR-alpha(1)-deficient mice exhibited significantly prolonged contraction and relaxation times (20-40%) in both twitches and tetani compared to controls.
- TR-beta-deficient mice showed reduced fatigue resistance but normal contraction/relaxation times, despite elevated thyroid hormone levels.
- Western blot analysis revealed decreased SERCa1 concentration in TR-alpha(1)-deficient muscles, but not in TR-beta-deficient muscles.
Conclusions:
- Both TR-alpha(1) and TR-beta are essential for a normal thyroid hormone response in skeletal muscle.
- TR-alpha(1) primarily influences the kinetics of muscle contraction and relaxation, partly via SERCa1 regulation.
- TR-beta contributes to maintaining skeletal muscle fatigue resistance.