Audesirk T, Cabell L, Kern M, Audesirk G
Biology Department, University of Colorado at Denver, PO Box 173364, Denver, CO 80217-3364, USA.
Neuroscience. 2003;121(4):927-34. doi: 10.1016/s0306-4522(03)00294-x.
We utilized morphometric analysis of 3 day cultures of hippocampal neurons to determine the effects of both estradiol and the synthetic estrogen receptor modulator raloxifene on several parameters of neuronal growth and differentiation. These measurements included survival, neurite production, dendrite number, and axon and dendrite length and branching. 17 beta-Estradiol (10 nM) selectively stimulated dendrite branching; this effect was neither mimicked by alpha-estradiol, nor blocked by the estrogen receptor antagonist ICI 182780. The selective estrogen receptor modulator raloxifene (100 nM) neither mimicked nor reversed the effects of estradiol on dendritic branching. Western immunoblotting for the alpha and beta subtypes of estrogen receptor revealed the presence of alpha, but not beta, estrogen receptors in our hippocampal cultures. There is growing recognition of the effects of 17 beta-estradiol on neuronal development and physiology, with implications for brain sexual dimorphism, plasticity, cognition, and the maintenance of cognitive function during aging. The role of estradiol in hippocampal neuronal differentiation and function has particular implications for learning and memory. These data support the hypothesis that 17 beta-estradiol is acting via alpha estrogen receptors in influencing hippocampal development in vitro. Raloxifene, prescribed to combat osteoporosis in post-menopausal women, is a selective estrogen receptor modulator with tissue-specific agonist/antagonist properties. Because raloxifene had no effect on dendritic branching, we hypothesize that it does not interact with the alpha estrogen receptor in this experimental paradigm.
我们利用对海马神经元3天培养物的形态计量分析，来确定雌二醇和合成雌激素受体调节剂雷洛昔芬对神经元生长和分化的几个参数的影响。这些测量包括存活率、神经突产生、树突数量以及轴突和树突的长度与分支。17β-雌二醇（10 nM）选择性地刺激树突分支；这种作用既不能被α-雌二醇模拟，也不能被雌激素受体拮抗剂ICI 182780阻断。选择性雌激素受体调节剂雷洛昔芬（100 nM）既不能模拟也不能逆转雌二醇对树突分支的影响。对雌激素受体α和β亚型进行的蛋白质免疫印迹分析显示，在我们的海马培养物中存在α雌激素受体，但不存在β雌激素受体。人们越来越认识到17β-雌二醇对神经元发育和生理学的影响，这对脑性二态性、可塑性、认知以及衰老过程中认知功能的维持具有重要意义。雌二醇在海马神经元分化和功能中的作用对学习和记忆具有特殊意义。这些数据支持了这样的假设，即17β-雌二醇通过α雌激素受体在体外影响海马发育。雷洛昔芬被用于治疗绝经后女性的骨质疏松症，是一种具有组织特异性激动剂/拮抗剂特性的选择性雌激素受体调节剂。由于雷洛昔芬对树突分支没有影响，我们假设在这个实验范式中它不与α雌激素受体相互作用。
