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

P. Venditti, G. Chiellini, L. Di Stefano, G. Napolitano, R. Zucchi, A. Columbano, T. S. Scanlan, S. Di Meo

Research output: Contribution to journalArticle

10 Scopus citations

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 TRb agonist. T3 treatment produces increases in O2 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 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 proliferatoractivated receptor-γ coactivator-1α suggest the involvement of respiratory factors in the agonist-linked changes in mitochondrial respiratory capacities and H2O2 production.

Original languageEnglish (US)
Pages (from-to)279-289
Number of pages11
JournalJournal of Endocrinology
Volume205
Issue number3
DOIs
StatePublished - Jun 1 2010

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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    Venditti, P., Chiellini, G., Di Stefano, L., Napolitano, G., Zucchi, R., Columbano, A., Scanlan, T. S., & Di Meo, S. (2010). The TRβ-selective agonist, GC-1, stimulates mitochondrial oxidative processes to a lesser extent than triiodothyronine. Journal of Endocrinology, 205(3), 279-289. https://doi.org/10.1677/JOE-10-0036