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17β-Estradiol alters oxidative stress response protein expression and oxidative damage in the uterus

Yuan, Lisi, Dietrich, Alicia K., Nardulli, Ann M.
Molecular and Cellular Endocrinology 2014 v.382 pp. 218-226
carcinogenesis, cell proliferation, endometrium, estradiol, females, lipid peroxidation, messenger RNA, mice, ovariectomy, oxidative stress, protein disulfide-isomerase, protein synthesis, proteins, reactive oxygen species, steroid hormones, stress response, superoxide dismutase
The steroid hormone 17β-estradiol (E2) has profound effects on the uterus. However, with the E2-induced increase in uterine cell proliferation and metabolism comes increased production of reactive oxygen species (ROS). We examined the expression of an interactive network of oxidative stress response proteins including thioredoxin (Trx), Cu/Zn superoxide dismutase (SOD1), apurinic endonuclease (Ape1), and protein disulfide isomerase (PDI). We demonstrated that treatment of ovariectomized C57BL/6J female mice with E2 increased the mRNA and protein levels of Trx, but decreased SOD1 and Ape1 mRNA and protein expression. In contrast, E2 treatment increased PDI protein levels but had no effect on PDI transcript levels. Interestingly, E2 treatment also increased two markers of cellular damage, lipid peroxidation and protein carbonylation. Our studies suggest that the decreased expression of SOD1 and Ape1 caused by E2 treatment may in the long term result in disruption of ROS regulation and play a role in endometrial carcinogenesis.