Changes in thyroid status are associated with profound alterations in 
biochemical and physiological functioning of cardiac muscle impacting metabolic 
rate, contractility and structural hypertrophy. Using an in vivo model of 
chronic treatment with thyroid hormone (T4, 0.3 mg/kg/day), we evaluated how 
mitochondria are regulated in response to T4, and assessed the relationship of 
T4-induced mitochondrial biogenesis and bioenergetics to overall cardiac 
hypertrophy. The role of thyroid hormone in cardiac bioenergetic remodeling was 
addressed in rats treated with T4 for 5, 10 and 15 days. Over that time, 
myocardial oxygen consumption substantially increased as did cardiac 
hypertrophy. Myocardial levels of mitochondrial enzyme activities, mitochondrial 
DNA (mtDNA), specific proteins and transcript were assessed. Activity levels of 
respiratory complexes I-V and citrate synthase significantly increased with 15 
but not with 5 or 10-day T4 treatment. Myocardial levels of mtDNA, mitochondrial 
proteins (e.g. cytochrome c, cytochrome b, ATPase subunits, MnSOD) and the 
global transcription factor PPARalpha were significantly elevated with 15-day 
T4. Transcript analysis revealed increased expression of transcription factors 
and cofactors involved in mitochondrial biogenesis including PPARalpha, mtTFA, 
ErbAalpha and PGC-1alpha. Our findings indicate parallel increases in myocardial 
mitochondrial bioenergetic capacity, oxygen consumption and markers of 
mitochondrial biogenesis with 15-day T4; these changes were not present with 
10-day T4 even with significant cardiac hypertrophy. The marked, parallel 
increases in PPARalpha levels suggest its potential involvement in mediating 
myocardial-specific remodeling of mitochondria in response to T4.