The gonadal steroid estrogen has been shown to affect neuronal growth,
differentiation and survival We examined the ability of estrogen to p
rotect primary cortical neurons from toxicity induced by the excitator
y neurotransmitter glutamate. In these experiments, a 24-h pretreatmen
t with 15 and 50 nM 17 beta-estradiol significantly reduced cellular l
actate dehydrogenase (LDH) release from primary cortical neurons, indi
cating that neurons treated with 17 beta-estradiol were protected from
a toxic glutamate exposure. Pretreatment with related steroids such a
s progesterone, dihydrotestosterone, dexamethasone or cholesterol did
not significantly decrease LDH release. The anti-estrogen tamoxifen bl
ocked the protective effects of 17 beta-estradiol suggesting that a cl
assical steroid hormone receptor may be involved in the mechanism subs
erving estrogen neuroprotection during glutamate toxicity.