Thyroid hormone response of slow and fast sarcoplasmic reticulum Ca 2+ ATPase mRNA in striated muscle

Abstract

The thyroid status markedly influences the contractile function of muscle, and changes in the activity of the Ca 2+ ATPase of the sarcoplasmic reticulum (SR) contribute to these alterations. Two separate genes encode the major isoforms of SR Ca 2+ ATPase. In fast skeletal muscle, sarcoplasmic endoplasmic reticulum Ca 2+ ATPase type 1 (SERCal) 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 Ca 2+ 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 (T 3) administration to hypothyroid rats. T 3 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, T 3 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. In hyperthyroid animals, soleus muscle exhibited a striking increase in SERCa1 mRNA to 252 ± 37% of control values, whereas SERCa2 mRNA was lowered to 72 ± 16% of control values. In hyperthyroid cardiac muscle, SERCa2 mRNA increases to 130 ± 8% of control values. Hyperthyroidism induced no change in SERCa1 mRNA of EDL but lowered SERCa2 mRNA to 61 ± 13% of control levels. In summary, acute and chronic changes in thyroid status lead to divergent muscle-type and gene-type specific responses of SERCa1 and SERCa2 mRNA.