Effect of hypothyroidism on satellite cells and postnatal fiber development in the soleus muscle of rat

Abstract

The effect of hypothyroidism, induced by 4-propyl-2-thiouracil, on muscle satellite cells in vivo and in vitro, and on postnatal muscle fiber development in the soleus muscle of rats during the first 40 days of postnatal life was analyzed. The proliferative activity of satellite cells was determined by means of bromodeoxyuridine incorporation. Creatine kinase activity was used as a marker for differentiation. In vivo, hypothyroidism resulted in smaller fibers in which the amount of sarcoplasm remained in balance with the number of myonuclei. The in vivo labeling data of satellite cells did not indicate a decreased proliferative activity, but the in vitro experiments showed that the hypothyroid rat muscles contained fewer satellite cells that were less active in proliferation and differentiation at the start of culture. Despite this, the bromodeoxyuridine signal increased in time at a similar rate as that in control cultures. From this and because the cells resembled control cells in their response to bFGF, we conclude that hypothyroid satellite cells remain responsive to proliferation stimuli. However, in hypothyroid cultures, the activity of creatine kinase is lower, even at longer culture times. We therefore conclude that hypothyroid status affects muscle precursor cells mainly by depressing their ability to differentiate and fuse with existing myofibers.