Lan Lee

17beta‐estradiol protects oligodendrocytes from cytotoxicity induced cell death

During pregnancy, changes in circulating levels of hormones, including estrogens, correlates with a significant decrease in the relapse incidence in women with Multiple Sclerosis (MS). In the present study, we demonstrate that both primary and cell line cultures of rat oligodendrocytes express the estrogen receptor (ER)‐α and ERβ estrogen receptors in the cytosol and nucleus, and that nuclear compartmentalization becomes more pronounced as the cells mature. Moreover, 17β‐estradiol significantly decreases the cytotoxic effects of the peroxynitrite generator 3‐(4‐morpholinyl)‐sydnonimine (SIN‐1) in both immature and mature oligodendrocytes in a dose dependent manner. This protective mechanism requires pretreatment with 17β‐estradiol and is blocked by ICI 182,780, a selective ERα/ERβ antagonist. These results strongly suggest that 17β‐estradiol protects oligodendrocytes against SIN‐1 mediated cytotoxicity through the activation of the estrogen receptors and provides new insights into the roles of the estrogen signaling pathways in myelin forming cells that are lost in demyelinating disorders.