1: Endocrinology. 2008 Jan;149(1):424-33. Epub 2007 Sep 20. Oxidative stress in the thyroid gland: from harmlessness to hazard depending on the iodine content. Poncin S, Gérard AC, Boucquey M, Senou M, Calderon PB, Knoops B, Lengelé B, Many MC, Colin IM. Unité de Morphologie Expérimentale (MOEX), Université catholique de Louvain, UCL-5251, 52 Avenue East Mounier, B-1200 Brussels, Belgium. ides.colin@moex.ucl.ac.be. In basal conditions, thyroid epithelial cells produce moderate amounts of reactive oxygen species (ROS) that are physiologically required for thyroid hormone synthesis. They are not necessarily toxic because they are continuously detoxified either in the process of hormone synthesis or by endogenous antioxidant systems. Using a rat model of goiter formation and iodine-induced involution, we found that compared with control thyroids, the oxidative stress, assessed by the detection of 4-hydroxynonenal, was strongly enhanced both in hyperplastic and involuting glands. The level of antioxidant defenses (glutathione peroxidases and peroxiredoxins) was also up-regulated in both groups, although somewhat less in the latter. Of note, increased oxidative stress came along with an inflammatory reaction, but only in involuting glands, suggesting that although antioxidant systems can adequately buffer a heavy load of ROS in goiter, it is not necessarily the case in involuting glands. The effects of 15-deoxy-Delta(12,14)-prostaglandin J2 (15dPGJ2), an endogenous ligand of peroxisome proliferated-activated receptor gamma (PPARgamma) with antiinflammatory properties, were then investigated in involuting glands. This drug strongly reduced both 4-hydroxynonenal staining and the inflammatory reaction, indicating that it can block iodine-induced cytotoxicity. When experiments were carried out with the PPARgamma antagonist, bisphenol A diglycidyl ether, 15dPGJ2-induced effects remained unchanged, suggesting that these effects were not mediated by PPARgamma. In conclusion, thyroid epithelial cells are well adapted to endogenously produced ROS in basal and goitrous conditions. In iodine-induced goiter involution, the increased oxidative stress is accompanied by inflammation that can be blocked by 15dPGJ2 through PPARgamma-independent protective effects. PMID: 17884933 [PubMed - in process] Related Links Inhibition of IFN-gamma-mediated inducible nitric oxide synthase induction by the peroxisome proliferator-activated receptor gamma agonist, 15-deoxy-delta 12,14-prostaglandin J2, involves inhibition of the upstream Janus kinase/STAT1 signaling pathway. [J Immunol. 2003] PMID:12847270 15-Deoxy-Delta12,14-prostaglandin J2 and peroxisome proliferator-activated receptor gamma (PPARgamma) levels in term placental tissues from control and diabetic rats: modulatory effects of a PPARgamma agonist on nitridergic and lipid placental metabolism. [Reprod Fertil Dev. 2005] PMID:15899154 Magnitude of peroxisome proliferator-activated receptor-gamma activation is associated with important and seemingly opposite biological responses in breast cancer cells. [J Investig Med. 2001] PMID:11523697 Apoptotic action of peroxisome proliferator-activated receptor-gamma activation in human non small-cell lung cancer is mediated via proline oxidase-induced reactive oxygen species formation. [Mol Pharmacol. 2007] PMID:17535976 Antioxidants, oxidative damage and oxygen deprivation stress: a review. [Ann Bot (Lond). 2003] PMID:12509339