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, B-1200 Brussels, Belgium. 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 - indexed for MEDLINE] Related Links [Effect of chronic mild and moderate iodine excess on thyroid anti-oxidative ability of iodine deficiency and non-iodine deficiency Wistar rats] [Zhonghua Yi Xue Za Zhi. 2006] PMID:16796889 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 Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution. [J Endocrinol. 2002] PMID:11834455 Increased follicular heterogeneity in experimental colloid goiter produced by refeeding iodine excess after thyroid hyperplasia. [Endocrinology. 1986] PMID:3943488 Transformation of normal thyroids into colloid goiters in rats and mice by diphenylthiohydantoin. [Endocrinology. 1994] PMID:7988459