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Am J Physiol Endocrinol Metab 274: E1018-E1026, 1998;
0193-1849/98 $5.00
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Vol. 274, Issue 6, E1018-E1026, June 1998

Thyroid receptor plasticity in striated muscle types: effects of altered thyroid state

Fadia Haddad, Anqi X. Qin, Samuel A. McCue, and Kenneth M. Baldwin

Department of Physiology and Biophysics, University of California, Irvine, California 92697

This study examined nuclear thyroid receptor (TR) maximum binding capacity (Bmax), dissociation constant (Kd), and TR isoform (alpha 1, alpha 2, beta 1) mRNA expression in rodent cardiac, "fast-twitch white," "fast-twitch red," and "slow-twitch red" muscle types as a function of thyroid state. These analyses were performed in the context of slow-twitch type I myosin heavy-chain (MHC) expression, a 3,5,3'-triiodothyronine (T3)-regulated gene that displays varying responsiveness to T3 in the above tissues. Nuclear T3 binding analyses show that the skeletal muscle types express more TRs per unit DNA than cardiac muscle, whereas the latter has a lower Kd than the former. Altered thyroid state had little effect on either cardiac Bmax or Kd, whereas hypothyroidism increased Bmax in the skeletal muscle types without affecting its Kd. Cardiac muscle demonstrated the greatest mRNA signal of TR-beta 1 compared with the other muscle types, whereas the TR-alpha 1 mRNA signals were more abundant in the skeletal muscle types, especially fast-twitch red. Hyperthyroidism increased the ratio of beta 1 to alpha 1 and decreased the ratio of alpha 2- to alpha 1+beta 1-mRNA signal across the muscle types, whereas hypothyroidism caused the opposite effects. The nuclear T3 affinity correlated significantly with the TR-beta 1 mRNA expression but not with TR-alpha 1 mRNA expression. Collectively, these findings suggest that, despite a divergent pattern of TR mRNA expression in the different muscle types, these patterns follow similar qualitative changes under altered thyroid state. Furthermore, TR expression pattern cannot account for the quantitative and qualitative changes in type I MHC expression that occur in the different muscle types.

heart; slow-twitch muscle; fast-twitch muscle; maximum binding capacity; hyperthyroidism; hypothyroidism; thyroid receptor mRNA


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