In order to analyze the role of thyroid hormones in mitochondrial biogenesis, we 
have studied the expression pattern of the beta subunit of the mitochondrial 
ATP-synthase complex in liver and in isolated mitochondria during postnatal 
development of hypothyroid rats. Chemically induced hypothyroidism promoted a 
significant reduction in body and liver masses at all stages of development. 
Furthermore, plasma 3,5,3'-triiodo-L-thyronine (T3) and 
3,5,3',5'-tetraiodo-L-thyronine (T4) concentrations were significantly reduced 
in hypothyroid animals when compared to euthyroid animals. Remarkably, 
steady-state beta-F1-ATPase mRNA levels in livers of hypothyroid animals showed 
an approximately 50% reduction when compared to age-matched euthyroid rats at 
all stages of development. The relative amounts of beta-F1-ATPase protein 
determined in isolated mitochondria of 1-day-old and adult hypothyroid animals 
were similar to those determined in mitochondria of age-matched euthyroids, 
indicating that hypothyroidism does not affect organelle differentiation in the 
liver of suckling and adult rats. In contrast, the relative amount of 
beta-F1-ATPase protein in liver homogenates varied (0-30% reduction) due to the 
hypothyroid condition during development. These findings suggest the existence 
of compensatory mechanisms operating at the translational and/or 
post-translational levels which promote proliferation of mitochondria in the 
hypothyroid liver. However, when the liver mass was considered, hypothyroidism 
significantly reduced overall mitochondrial proliferation in rat liver. 
Interestingly, the effects of thyroid hormones on the biogenesis of the ATP 
synthase complex at latter stages of development provide an example in which the 
hypothyroid condition limits the expression of the nuclear-encoded gene with no 
apparent effect on the expression of the mitochondrial-encoded genes (ATP 
synthase subunits 6-8).