Modulation of sympathetic nervous system by environmental estrogens : Molecular and pharmacological analysis in adrenal medulla

环境雌激素是一种非类固醇的人造化学物质，可以通过摄取或吸收进入人体，并模仿雌激素的作用。据报道，环境雌激素通过与核类固醇受体相互作用来调节性分化。人们的注意力一直集中在生殖器官上，但性类固醇的作用要广泛得多。已有报道雌激素通过非基因组机制调节神经递质受体、转运体和离子通道的功能。为探讨环境雌激素对神经内分泌系统的影响，我们观察了双酚A和壬基酚对培养的牛肾上腺髓质细胞儿茶酚胺分泌和摄取的影响。双酚A显著抑制细胞对去甲肾上腺素的摄取(1~100μM)。这种影响与运输过程的最大速度降低有关，而t…没有明显变化。米氏-曼腾常数越大。用17β-雌二醇处理细胞后，双酚A对去甲肾上腺素转运体活性的抑制作用重现。Scatchard分析表明，双酚A降低了最大结合量，增加了解离常数。双酚A以浓度依赖的方式抑制卡巴胆碱诱导的儿茶酚胺分泌、钙内流和钠内流(10-100μM)。它还以浓度依赖的方式抑制藜芦碱和高K诱导的反应。以浓度(10-100μM)和时间(2-72 h)依赖的方式激活烟碱型乙酰胆碱受体，能显著抑制卡巴胆碱诱导的儿茶酚胺分泌和钙内流。它还通过激活电压依赖性钠通道抑制藜芦碱诱导的反应，而对高钾引起的儿茶酚胺分泌影响不大。这些结果表明，环境雌激素通过非基因组方式抑制受体、离子通道和转运体来调节交感神经活动。较少

Environmental estrogens are nonsteroidal manmade chemicals that can enter the body by ingestion or absorption and mimic the action of estrogens. Environmental estrogens have been reported to modulate sexual differentiation by interacting with nuclear steroid receptors. The focus has been on reproductive organs, but sex steroids have far more widespread actions. Estrogen has been reported to modulate the function of neurotransmitter receptors, transporters and ionic channels via nongenomic mechanisms. In the present study, to investigate the influence of environmental estrogens on neuro-endocrine system, we examined the effects of bisphenol A and nonylphenol on catecholamine secretion and uptake in cultured bovine adrenal medullary cells.Bisphenol A significantly inhibited the uptake of [^3H] noradrenaline by the cells in a concentration-dependent manner (1-100 μM). The effect was associated with a decrease in the maximal velocity of the transport process with no significant change in t … More he Michaelis-Menten constant. Treatment of the cells with 17β-estradiol reproduced the inhibitory effects of bisphenol A on the norepinephrine transporter activity. Scatchard analysis of [^3H] desipramine binding revealed that bisphenol A decreased the maximal binding and increased the dissociation constant. Bisphenol A inhibited carbachol-induced catecholamine secretion, ^<45>Ca and ^<22>Na influx in a concentration-dependent manner (10-100 μM). It also inhibited veratridine and high K-induced responses in a concentration-dependent manner. Treatment of the cells with nonylphenol led to a significant inhibition of carbachol-induced catecholamine secretion and ^<45>Ca influx via an activation of nicotinic acetylcholine receptor in a concentration (10-100 μM) - and time (2-72 h) - dependent manner. It also inhibited veratridine-induced responses via an activation of voltage-dependent Na channels, whereas it had little effect on catecholamine secretion caused by high K, a direct activation of voltage-dependent Ca channels.These results suggest that environmental estrogens modulate the sympathetic nervous activity through inhibition of receptor, ion channel and transporter in non-genomic manner. Less