Patisaul H B, Whitten P L, Young L J
Population Biology and Evolutionary Ecology Program, Emory University, Atlanta GA, 30322, USA.
Brain Res Mol Brain Res. 1999 Apr 6;67(1):165-71. doi: 10.1016/s0169-328x(99)00058-3.
Estrogen receptor alpha (ERalpha) and estrogen receptor beta (ERbeta) are differentially distributed in the brain and likely mediate different estrogen-dependent processes. ERbeta is abundant in the bed nucleus of the stria terminalis, medial preoptic nucleus, paraventricular nucleus of the hypothalamus and the amygdala of the rat. In the paraventricular nucleus, which is devoid of ERalpha, ERbeta is colocalized with the neuropeptides, oxytocin and vasopressin, suggesting a potential functional role for ERbeta in the regulation of these peptides. We examined the regulation of ERbeta mRNA expression in the rat brain by 17beta-estradiol and the phytoestrogen, coumestrol. 17beta-Estradiol treatment decreased ERbeta mRNA in situ hybridization signal by 44.5% in the paraventricular nucleus of the hypothalamus (PVN), but had no effect in the bed nucleus of the stria terminalis (BnST) or the medial preoptic nucleus (MPA). In contrast, dietary exposure to coumestrol increased ERbeta mRNA signal by 47.5% in the PVN but had no effect in the BnST or the MPA. These data demonstrate that like ERalpha, ERbeta is down regulated by estrogen in a region specific manner in the rat brain. Furthermore, exposure to coumestrol may modulate ERbeta-dependent processes by acting as an anti-estrogen at ERbeta. This data contradicts results from cell transfection assays which suggest an estrogenic activity of coumestrol on ERbeta, indicating that the mode of action may be tissue specific, or that metabolism of dietary coumestrol may alter its effects. Because the highest concentrations of phytoestrogens are found in legumes, vegetables and grains, they are most prevalent in vegetarian and traditional Asian diets. Understanding the neuroendocrine effects of phytoestrogens is particularly important now that they are being marketed as a natural alternative to estrogen replacement therapy and sold in highly concentrated pills and powders.
雌激素受体α（ERα）和雌激素受体β（ERβ）在大脑中的分布存在差异，可能介导不同的雌激素依赖过程。ERβ在大鼠终纹床核、内侧视前核、下丘脑室旁核和杏仁核中含量丰富。在缺乏ERα的室旁核中，ERβ与神经肽催产素和加压素共定位，这表明ERβ在调节这些肽方面可能具有潜在的功能作用。我们研究了17β-雌二醇和植物雌激素香豆雌酚对大鼠大脑中ERβ mRNA表达的调节作用。17β-雌二醇处理使下丘脑室旁核（PVN）中的ERβ mRNA原位杂交信号降低了44.5%，但对终纹床核（BnST）或内侧视前核（MPA）没有影响。相比之下，饮食中摄入香豆雌酚使PVN中的ERβ mRNA信号增加了47.5%，但对BnST或MPA没有影响。这些数据表明，与ERα一样，ERβ在大鼠大脑中也以区域特异性方式被雌激素下调。此外，摄入香豆雌酚可能通过作为ERβ的抗雌激素来调节ERβ依赖的过程。这一数据与细胞转染实验的结果相矛盾，细胞转染实验表明香豆雌酚对ERβ具有雌激素活性，这表明其作用方式可能具有组织特异性，或者饮食中香豆雌酚的代谢可能会改变其作用效果。由于植物雌激素在豆类、蔬菜和谷物中含量最高，它们在素食和传统亚洲饮食中最为常见。鉴于植物雌激素正作为雌激素替代疗法的天然替代品进行销售，并以高浓缩药丸和粉末的形式出售，了解其神经内分泌作用尤为重要。
