Effects of phytoestrogens on neuronal functions in noradrenergic neurons during early life : Basic studies for risk assesment

有相当多的证据表明，雌激素和植物雌激素在预防心血管疾病和抑制肿瘤生长方面具有有益的作用。虽然雌激素也被报道可以防止氧化损伤引起的神经元变性，但植物雌激素是否会影响去甲肾上腺素能和5-羟色胺能神经元的功能仍不清楚。因此，我们研究了植物雌激素对儿茶酚胺合成、分泌和再摄取的影响。白藜芦醇和大豆苷元抑制乙酰胆碱(ACh)诱导的儿茶酚胺分泌和内流。白藜芦醇直接抑制ACh在表达3b4神经元烟碱型乙酰胆碱受体的非洲爪哇卵母细胞上诱发的电流。低浓度大豆苷元(10 nm~1μM)通过质膜雌激素受体刺激儿茶酚胺的合成。经典的雌激素受体抑制剂IC1182、780不能抑制这种刺激作用。Genistein以浓度依赖的方式刺激去甲肾上腺素转运体(Net)和5-羟色胺转运体(SERT)的功能(10 nm-10rM)。其他异黄酮类，如大豆苷元和孜然雌酚，效果不大。金雀异黄素的这种刺激作用改变了质膜中Net数目的增加。这些发现表明植物雌激素在去甲肾上腺素能神经元的神经功能调节中发挥作用。为了确定植物雌激素对儿茶酚胺能神经元的影响和风险，还需要对小鼠体内给予植物雌激素的进一步研究。

There is considerable evidence to indicate that estrogens and phytoestrogens have beneficial effects on protection against cardiovascular diseases and on the inhibition of tumor growth. Although estrogens also have been reported to prevent neuronal degeneration caused by oxidative damage, it remains unknown whether the phytoestrogen could affect the functions of the noradrenergic and serotonergic neurons. Therefore, we investigated the effect of phytoestrogens on the catecholamine synthesis, secretion and reuptake. Resveratrol and Daidzein suppressed catecholamine secretion and ^<22>Na^+^ and ^<45>Ca^<2+> influx induced by acetylcholine (ACh). Resveratrol directly inhibited the current evoked by ACh in Xenopus oocytes expressing a3b4 neuronal nicotinic acetylcholine receptor. Daidzein at low concentration (10nM〜1μM) stimulates catecholamine synthesis through plasma membrane estrogen receptors. This stimulatory effect was not inhibited by IC1182, 780, a classical estrogen receptor inhibitor.Genistein was stimulated the functions of norepinephrine transporter (NET) and serotonin transporter (SERT) in a concentration-dependent manner (10nM-10RM). Other isoflavones, such as daidzein and cumestrol, had little effect. This stimulatory effect of genistein was altering an increase in the number of NET in the plasma membrane.These findings suggest that phytoestrogens play a role in the regulation of neuronal functions on noradrenergic neurons. To confirm the effects and risks of phytoestrogens on catecholaminergic neurons, further in vivo studies of the administration of phytoestrogens to mice are required.