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Thyroid hormone response of slow and fast sarcoplasmic reticulum Ca2+ ATPase mRNA in striated muscle
M R Sayen1, D K Rohrer, W H Dillmann
1Department of Medicine, University of California, San Diego 92103.
Abstract:
The thyroid status markedly influences the contractile function of muscle, and changes in the activity of the Ca2+ ATPase of the sarcoplasmic reticulum (SR) contribute to these alterations. Two separate genes encode the major isoforms of SR Ca2+ ATPase. In fast skeletal muscle, sarcoplasmic endoplasmic reticulum Ca2+ ATPase type 1 (SERCa1) presents the major isoform, whereas in slow skeletal muscle SERCa type 2 (SERCa2) predominates. Cardiac muscle contains only SERCa2. To examine the mechanisms responsible for changes in contractile function, we quantitated SERCa1 and SERCa2 mRNA levels in fast extensor digitorum longus muscle (EDL), slow soleus muscle, and cardiac muscle in rats of different thyroid status. Hypothyroidism led in soleus to a marked decrease in SERCa1 mRNA and SERCa2 mRNA levels, in cardiac muscle SERCa2 mRNA decreased markedly, as previously shown by us, and in EDL SERCa1 mRNA decreased. These findings are compatible with a hypothyroidism induced decrease in SR Ca2+ ATPase activity and a delay in muscle relaxation. In contrast, SERCa2 mRNA of EDL, representing only a small percent of total SERCa mRNA in this muscle, increased to 175% of control values. Muscle specific and SERCa gene specific changes also occur after acute triiodothyronine (T3) administration to hypothyroid rats. T3 does not induce a significant change in SERCa1 or SERCa2 mRNA levels in soleus, but in the heart SERCa2 mRNA increases about 3-fold. In EDL, T3 increases SERCa1 mRNA from a hypothyroid level of 59 +/- 6% to 138 +/- 4% of control values but SERCa2 mRNA is decreased to 75 +/- 5% of control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Thyroid status impacts muscle function by altering sarcoplasmic reticulum Ca2+ ATPase (SERCa) mRNA levels. Hypothyroidism decreases SERCa1 and SERCa2 mRNA in slow and fast muscles, affecting muscle relaxation.
Area of Science:
- Endocrinology
- Molecular Biology
- Muscle Physiology
Background:
- Thyroid hormones significantly influence skeletal and cardiac muscle contractile function.
- Sarcoplasmic reticulum Ca2+ ATPase (SR Ca2+ ATPase) activity is crucial for muscle relaxation and is modulated by thyroid status.
- Two main isoforms, SERCa1 and SERCa2, encoded by separate genes, predominate in different muscle types.
Purpose of the Study:
- To investigate the impact of thyroid status on SERCa1 and SERCa2 mRNA expression in distinct rat muscles (fast EDL, slow soleus, cardiac).
- To elucidate the molecular mechanisms underlying thyroid-induced alterations in muscle contractile function.
Main Methods:
- Quantitative analysis of SERCa1 and SERCa2 mRNA levels in rat extensor digitorum longus (EDL), soleus, and cardiac muscles.
- Assessment of mRNA changes in hypothyroid rats and following triiodothyronine (T3) administration.
Main Results:
- Hypothyroidism significantly decreased SERCa1 and SERCa2 mRNA in soleus and cardiac muscle, and SERCa1 mRNA in EDL.
- In contrast, hypothyroidism led to an increase in SERCa2 mRNA in EDL.
- T3 administration to hypothyroid rats differentially affected SERCa mRNA levels, increasing cardiac SERCa2 and EDL SERCa1, while decreasing EDL SERCa2.
Conclusions:
- Thyroid status profoundly influences muscle-specific SERCa isoform gene expression.
- Observed changes in SERCa mRNA levels correlate with altered SR Ca2+ ATPase activity, potentially explaining thyroid-related effects on muscle relaxation.
- Differential regulation of SERCa isoforms by thyroid hormones highlights tissue-specific adaptive mechanisms.