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Thyroid hormone increased the percentage of fibers expressing fast-type sarcoplasmic reticulum Ca(2+)-ATPase in the slow rat soleus muscle from 17% in the hypothyroid to 100% in the hyperthyroid state. This was accompanied by a 12-fold increase in the fast-type Ca(2+)-ATPase protein content of soleus muscle homogenates, suggesting that also the amount of this protein per muscle fiber was increased. In contrast to the fast-type isoform, a decrease in the percentage of fibers expressing slow-type Ca(2+)-ATPase from 100% to 70% was observed in the transition from the hypothyroid to the hyperthyroid state. Slow-type Ca(2+)-ATPase protein levels in muscle homogenates however did not decrease on the same trajectory, but were even elevated in the euthyroid state. In the fast extensor digitorum longus muscle qualitatively similar changes in Ca(2+)-ATPase isoform expression were observed. The results suggest a dual action of thyroid hormone: 1. increasing slow-type Ca(2+)-ATPase expression in individual fibers 2. decreasing the fraction of slow-type Ca(2+)-ATPase expressing fibers.

In gastrocnemius muscle from newborn rats the mRNA for the fast sarcoplasmic reticulum (SR) Ca(2+)-ATPase isoform (SERCA1) comprised over 90% of total SR Ca(2+)-ATPase mRNA content and increased 5-fold between day 5 and 20 after birth, whereas in hypothyroid muscle the SERCA1 message level remained constant. Triiodothyronine (T3) treatment of 2-day-old euthyroid rats induced a precocious stimulation of SERCA1 mRNA levels, indicating that T3 is the determining factor in the stimulation of SERCA1 message levels and that this stimulation underlies the previously reported effect of the thyroid status on the neonatal development of SR Ca(2+)-ATPase activity. The low mRNA level for the slow SR Ca(2+)-ATPase isoform (SERCA2) was constant in both euthyroid and hypothyroid muscle development. Nevertheless, T3 treatment of hypothyroid neonates induced a transient stimulation of SERCA2 message levels, indicating that SERCA2 is responsive to higher levels of T3.

mRNA levels for the type I and type II isoforms of sarcoplasmic reticulum (SR) Ca-ATPase were determined in soleus (SOL) and extensor digitorum longus (EDL) muscle of euthyroid (normal), hypothyroid, and hyperthyroid rats. Total Ca-ATPase mRNA content of hyperthyroid muscle was 1.5-fold (EDL) and 6-fold (SOL) higher compared to hypothyroid muscle, with corresponding increases in total SR Ca-ATPase activity. EDL contained only type II Ca-ATPase mRNA. In SOL type I mRNA was the major form in hypothyroidism (98%), but the type II mRNA content was stimulated 150-fold by T3, accounting for 50% of the Ca-ATPase mRNA in hyperthyroidism.