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

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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.