Protective action of 17beta-estradiol and tamoxifen on glutamate toxicity in glial cells.

Estrogens influence differentiation, growth and function of neurons, but less is known of their effects on glia. In our experiments reported here, the ovarian steroid, 17beta-estradiol, and the "designer", non-steroidal estrogen, tamoxifen, effectively protected C-6 glioma 2B clone cells from the cytotoxicity of the excitatory neurotransmitter, glutamate. Exposure of these cells to 10-20 mM glutamate induced 61-78% cell death. Pre-treatment of the cells with 0.01 mM estradiol or with 2 microM tamoxifen significantly reduced the glutamate-induced cell death, estradiol being the most effective in this regard. Estradiol- or tamoxifen-treated cells that had survived glutamate damage appeared more mature than controls. Thus, estrogens often used in therapy (estradiol as replacement after menopause and tamoxifen for treatment/prevention of breast cancer) may significantly protect glial cells against glutamate toxicity and stimulate cell differentiation.