Isometric force and endurance in soleus muscle of thyroid hormone receptor-alpha 1- or -beta -deficient mice

Departments of 1 Physiology and Pharmacology and 3 Cellular and Molecular Biology, Karolinska Institute, S-171 77 Stockholm, Sweden; and 2 Institute for Experimental Medical Research, Ullevaal Hospital, Oslo, Norway The specific role of each subtype of thyroid hormone receptor (TR) on skeletal muscle function is unclear. We have therefore studied kinetics of isometric twitches and tetani as well as fatigue resistance in isolated soleus muscles of R- 1 - or - -deficient mice. The results show 20-40% longer contraction and relaxation times of twitches and tetani in soleus muscles from TR- 1 -deficient mice compared with their wild-type controls. TR- -deficient mice, which have high thyroid hormone levels, were less fatigue resistant than their wild-type controls, but contraction and relaxation times were not different. Western blot analyses showed a reduced concentration of the fast-type sarcoplasmic reticulum Ca 2+ -ATPase (SERCa1) in TR- 1 -deficient mice, but no changes were observed in TR- -deficient mice compared with their respective controls. We conclude that in skeletal muscle, both TR- 1 and TR- are required to get a normal thyroid hormone response. skeletal muscle; tetanic force; contraction; relaxation; fatigue