17α-Estradiol: A Brain-Active Estrogen?
2005
The estrogen 17β-estradiol has profound effects on the brain throughout life, whereas 17α-estradiol, the natural optical isomer, is generally considered less active because it binds less avidly to estrogen receptors. On the contrary, recent studies in the brain document that 17α-estradiol elicits rapid and sustained activation of the MAPK/ERK and phosphatidylinositol 3-kinase-Akt signaling pathways; is neuroprotective, after an ischemic stroke and oxidative stress, and in transgenic mice with Alzheimer’s disease; and influences spatial memory and hippocampal-dependent synaptic plasticity. The present study measured the endogenous content of 17α-estradiol in the brain and further clarified its actions and kinetics. Here we report that: 1) endogenous levels of 17α-estradiol and its precursor estrone are significantly elevated in the postnatal and adult mouse brain and adrenal gland of both sexes, as determined by liquid chromatography/tandem mass spectrometry; 2) 17α-estradiol and 17β-estradiol bind estroge...
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