INTERACTION OF THYROID-HORMONE AND FUNCTIONAL OVERLOAD ON SKELETAL-MUSCLE ISOMYOSIN EXPRESSION

This study examined the interaction of exogenous thyroid hormone 3,5,3 '-triiodothyronine (T-3) and functional overload on skeletal muscle my osin heavy chain (MHC) expression, studied at both the protein and mRN A level of analysis. Animals were allocated to the following groups: 1 ) normal control, 2) overload control, 3) hyperthyroid control, and 4) hyperthyroid + overload. Overload of the rat plantaris was accomplish ed by surgical removal of its synergists (soleus and gastrocnemius), a nd the animals were made hyperthyroid by injections of T-3 (350 mu g/k g every other day). After overload of 8 wk, muscle enlargement occurre d by 53% for both overload groups (P < 0.05). This was accompanied by a 330 and 82% increase in the relative content of type I and IIa MHC, respectively, and a corresponding decrease by 16 and 44% in type IIx a nd In, MHC, respectively, in the overload control group (P < 0.05 vs. normal control). Changes in the relative and absolute content of mRNA for these MHCs paralleled the protein response. Exogenous T-3 complete ly reversed the upregulation of type I MHC and the downregulation of t ype IIx associated with overload at both the protein and mRNA level (P < 0.05). However, T-3 was only partially effective in blunting the do wnregulation of IIb MHC and the upregulation of IIa MHC (protein and m RNA) accompanying the overload. These data suggest the following: 1) T -3 can override the overload-induced signal in upregulating type I MHC expression in fast muscle, 2) the faster IIx and IIb MHC pools are di fferentially regulated by T-3 and mechanical loading, and 3) both T-3 and mechanical loading likely exert their impact on MHC expression at the pretranslational level of regulation.