Effets neuroprotecteurs des composes estrogeniques des estrogenes conjugues equins (ECE)

The most frequently prescribed estrogen replacement therapy in the United States for postmenopausal women is a complex formulation of conjugated equine estrogens (CEE) under the trade name, Premarin®. Previous studies from our laboratory have demonstrated that CEE exerted significant neurotrophic and neuroprotective effects in neurons affected in Alzheimer's disease. In the present study, we have sought to determine which of the estrogenic components within CEE contribute to the neuroprotective effects of this complex formulation. Basal forebrain neurons were obtained from E18 rat brains and maintained in culture for 10 days. Individual equine estrogens were applied to cultured neurons for 3-4 days prior to exposure to either b-amyloid or excitotoxic levels of glutamate. As indicators of neuronal damage and viability, LDH, ATP or MTT assays were performed. Results of these analyses indicate that 17α-estradiol, 17β-estradiol, equilin, 17α-dihydroequilin, equilinen, 17α-dihydroequilenin, 17β-dihydroequilenin, and Δ^8,9-dehydroestrone exerted significant neuroprotective effects by reducing plasma membrane damage whereas estrone and 17β-dihydroequilin were ineffective. Combinations of neuroprotective estrogens could extend the range of neuroprotection from protecting against plasma membrane damage to promoting neuronal viability. These data suggest that select equine estrogens in CEE contribute to its neuroprotective effects and may be responsible for its ability to reduce the risk of developing Alzheimer's disease.