The TRbeta-selective agonist, GC-1, stimulates mitochondrial oxidative processes to a lesser extent than triiodothyronine.

Specific tissue responses to thyroid hormone are mediated by the hormone binding to two subtypes of nuclear receptors, TR alpha and TR beta. We investigated the relationship between TR beta activation and liver oxidative metabolism in hypothyroid rats treated with equimolar doses of triiodothyronine (T-3) and GC-1, a TR beta agonist. T-3 treatment produces increases in O-2 consumption and H2O2 production higher than those elicited by GC-1. The greater effects of T-3 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 TR alpha 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 T-3-treated rats are consistent with their higher lipid and protein oxidative damage and lower resistance to Ca2+ load. The T-3 and GC-1 effects on the expression levels of nuclear respiratory factor-1 and -2 and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha suggest the involvement of respiratory factors in the agonist-linked changes in mitochondrial respiratory capacities and H2O2 production. Journal of Endocrinology (2010) 205, 279-289