The Postnatal Development of Sarcoplasmic Reticulum Ca2+Transport Activity in Skeletal Muscle of the Rat is Critically Dependent on Thyroid Hormone

Abstract

We investigated the role of thyroid hormone in the postnatal development of Ca2+ transport activity of sarcoplasmic reticulum in skeletal muscle (m. gastrocnemius-plantaris). With a Ca2+-stat method using the fluorescent dye fura 2 as Ca2+ indicator, we determined the oxalate-supported maximal Ca2+ uptake activity of sarcoplasmic reticulum in whole muscle homogenates from neonatal rats. Expressed per g tissue wet wt, the activity increased nearly 10-fold during the first 8 weeks after birth, following which time a plateau was reached. This development was absent in hypothyroid pups, in which the level of Ca2+ uptake activity remained constant at 10% of the normal adult value for at least 8 weeks. When the mothers were given 0.05% propylthiouracil in the drinking water 1 week before parturition, these-pups ceased to grow after 4 weeks, had a reduced muscle protein content and a characteristic cretinous appearance. The effects of hypothyroidism could be reversed by T4 treatment (0.5 .mu.g/100 g BW, daily) starting 1 or 6 weeks after birth. Treatment with bovine GH (0.1 to 0.5 IU/100 g BW; daily) starting on day 5 stimlated body growth, particularly of muscle, but was without effect on the failing development of Ca2+ uptake activity. The postnatal rise in citrate synthase and succinate dehydrogenase activities was impaired in the hypothyroid group, but lactate dehydrogenase and creatine kinase activities rose continuously, although at a reduced rate. T3 treatment also reversed these effects of propylthoouracil. At the higher dosage used bovine GH appeared to stimulate the accumulation of creatine kinase. We conclude that the failing postnatal development of sarcoplasmic reticulum Ca2+ transport activity in hypothyroidism is not secondary to the absence of GH, nor is it part of a general, indiscriminate effect, but, rather, that it indicates an absolute requirement of thyroid hormone for this particular aspect of muscle differentiation.