Estrogen and the brain -: Beyond ER-α, ER-β, and 17β-estradiol
Estrogen and the brain -: Beyond ER-α, ER-β, and 17β-estradiol
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DOI：
10.1196/annals.1347.009
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发表时间：
2005-01-01
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影响因子：
--
通讯作者：
Toran-Allerand, CD
中科院分区：
文献类型：
--
作者：
Toran-Allerand, CD
The brain of both sexes is a major target of estradiol and a site of estrogen synthesis during development and in the adult. In addition to the classical intranuclear estrogen receptors (ERs) ER-alpha and ER-beta, we have recently identified a novel, plasma membrane-associated ER that is neither ER-alpha nor ER-beta in the brain and uterus, which we have designated "ER-X". ER-X is a developmentally regulated estrogen-binding protein that is present in wild-type, ER-alpha gene-disrupted (alpha ERKO) and ER-alpha-null mice. ER-X is re-expressed after ischemic brain injury and in adult transgenic mice with Alzheimer's disease. Although ER-X shares some homology with the C-terminal region of ER-alpha, it is not an alternative splicing variant of ER-a. and may be a new gene. ER-X mediates 17 alpha-estradiol and 17 beta-estradiol activation of MAPK/ERK. In contrast, ER-alpha does not elicit ERK activation but, surprisingly, is inhibitory. The potential importance of 17 alpha-estradiol, the preferred ligand of ER-X, for the brain is underscored by our findings by liquid chromatography/tandem mass spectrometry that the endogenous levels of 17 alpha-estradiol are significantly elevated in the postnatal day-7 and adult mouse neocortex and hippocampus, as compared with 17 beta-estradiol. That there is so much more 17 alpha-estradiol than 17 beta-estradiol in the brain suggests that this enantiomer would be readily available to the brain. In considering estrogens for postmenopausal treatment, one should consider all the ERs present in the brain, not just ER-alpha and ER-beta, but ER-X as well, and focus on ligands such as 17 alpha-estradiol that may be more selective for this ER.
