Estrogen protects primary cortical neurons from glutamate toxicity.

The gonadal steroid estrogen has been shown to affect neuronal growth, differentiation and survival. We examined the ability of estrogen to protect primary cortical neurons from toxicity induced by the excitatory neurotransmitter glutamate. In these experiments, a 24-h pretreatment with 15 and 50 nM 17 beta-estradiol significantly reduced cellular lactate dehydrogenase (LDH) release from primary cortical neurons, indicating that neurons treated with 17 beta-estradiol were protected from a toxic glutamate exposure. Pretreatment with related steroids such as progesterone, dihydrotestosterone, dexamethasone or cholesterol did not significantly decrease LDH release. The anti-estrogen tamoxifen blocked the protective effects of 17 beta-estradiol suggesting that a classical steroid hormone receptor may be involved in the mechanism subserving estrogen neuroprotection during glutamate toxicity.