Differential effects of Glucocorticoids and gonadal steroids on glutathione levels in neuronal and glial cell systems

The aim of the present study was to investigate the short and long-term effects of glucocorticoids [corticosterone (CORT), dexamethasone (DEX), 6-methylprednisolone (6-MP)] and gonadal steroids [17beta-estradiol (E-2), progesterone (PROG), testosterone (TEST)] on the levels of the antioxidant glutathione (GSH) in different cell systems of the CNS (neuronal hippocampal HT22 cells, primary hippocampal and neocortical brain cells, and C-6 glioma cells). In HT22 cells, steroids exerted mainly long-term effects. Significant increases of GSH levels were detectable after a 24 hr treatment with 10(-7) M of DEX (122% +/- 5%), 6-MP (208% +/- 32%), E-2 (134% +/- 10%), and TEST (155% +/- 17%). A significant decrease occurred after incubation with PROG for 24 hr (79% +/- 9%). In primary hippocampal cultures, a 24 hr treatment with DEX (140% +/- 8%), E-2 (123% +/- 6%), and PROG (118% +/- 5%) led to significant increases of the GSH levels, whereas, in neocortical primary cultures, only an incubation with E2 increased GSH (149% +/- 8%). In C-6 cells, hormone treatment led to both significant short-term (1 hr: CORT 114% +/- 5%, DEX 90% +/- 3%, E-2 88% +/- 3%; 3 hr: DEX 115% 5%, E-2 122% +/- 6%, TEST 78% +/- 4%) and significant long-term (24 hr: CORT 74% +/- 4%, 6-MP 84% +/- 5%, E-2 115% +/- 6%, PROG 91% +/- 4%, TEST 116% +/- 5%) effects. In summary, we were able to demonstrate differential effects of steroids on GSH levels in different cellular CNS models, showing an important influence of steroids and especially E-2 on antioxidative cellular functions in neuronal and glial cells. (C) 2002 Wiley-Liss, Inc.