Abstract

Specific tissue responses to thyroid hormone are mediated by the hormone binding to two subtypes of nuclear receptors, TRα and TRβ. We investigated the relationship between TRβ activation and liver oxidative metabolism in hypothyroid rats treated with equimolar doses of triiodothyronine (T₃) and GC-1, a TRβ agonist. T₃ treatment produces increases in O₂ consumption and H₂O₂ production higher than those elicited by GC-1. The greater effects of T₃ on oxidative processes are linked to the higher hormonal stimulation of the content of respiratory chain components including autoxidizable electron carriers as demonstrated by the measurement of activities of respiratory complexes and H₂O₂ generation in the presence of respiratory inhibitors. It is conceivable that these differential effects are dependent on the inability of GC-1 to stimulate TRα receptors that are likely involved in the expression of some components of the respiratory chain. The greater increases in reactive oxygen species production and susceptibility to oxidants exhibited by mitochondria from T₃-treated rats are consistent with their higher lipid and protein oxidative damage and lower resistance to Ca²⁺ load. The T₃ and GC-1 effects on the expression levels of nuclear respiratory factor-1 and -2 and peroxisome proliferator-activated receptor-γ coactivator-1α suggest the involvement of respiratory factors in the agonist-linked changes in mitochondrial respiratory capacities and H₂O₂ production.