Phospholipid hydroperoxide glutathione peroxidase gene is regulated via an estrogen and estrogen receptor signaling in cultured mouse fetuses

Abstract

Although it has been suggested that the transcription of phospholipid hydroperoxide glutathione peroxidase (PHGPx), an essential antioxidant selenoenzyme, may be affected by the estrogen state in mammals, the direct mechanism underlying the regulation of the PHGPx gene by estrogens in mammalian tissues remains to be clearly elucidated. In this study, we evaluated the expression of the PHGPx mRNA in cultured mouse fetuses (embryonic days 8.5-10.5) exposed to 17β-estradiol (E(2); 0.1, 1, 10, 100, and 1,000 ng/ml); estrogen receptor (ER) agonists [propyl pyrazole triol (PPT, an ERα-selective ligand, 1 μl/ml) and diarylpropionitrile (DPN, an ERβ-selective ligand, 1 μl/ml)]; and/or ER antagonist [ICI 182,780 (ICI, 1 μl/ml)] using a whole embryo culture system. E(2)-alone treatment significantly stimulated the expressions of both ERα and ERβ mRNAs in all the cultured fetuses (p < 0.05), although the ERβ mRNA levels were higher than ERα mRNA. PHGPx mRNA expression was significantly increased in all the fetuses treated with E(2) (1-1,000 ng/ml), PPT, and DPN (p < 0.05). Furthermore, pretreatment with ICI completely blocked the E(2)-induced PHGPx mRNA expression in the fetuses. In addition, the mRNA levels of cytosolic GPx, the other intracellular antioxidant selenoenzyme, did not differ significantly from the controls by an exposure to those agents. These results suggest that the PHGPx gene is regulated via an estrogen and ER signal pathway in the cultured mouse fetus.