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The direct action of estrone on vascular tissue involves genomic and non-genomic actions

机译：雌酮对血管组织的直接作用涉及基因组和非基因组作用

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A two step model mechanism of steroid action has been recently postulated. In this study, we test the hypothesis that, the biochemical action of estrone (E I) on vascular tissue could be performed via genomic and non-genomic actions. Rat aortic rings or vascular smooth muscle cell cultures (VSMC) were used to test the effect of the hormone on nitric oxide (NO) production, protein kinases activities and cell proliferation. Our data showed that estrone increased NO synthesis between 30 s and 20 min treatment, and this stimulatory effect was dependent on MAPK cascade activation, since it was prevented in the presence of a MAPK inhibitor (PD98059). Using a phosphorylation assay, we also showed that E, significantly increased MAPK activity. The effect of the hormone on PKC activity was measured in concentrations and time course studies. Direct treatment of rat aortic homogenates with E, significantly enhanced PKC activity (1-10 fold increase, p<0.01) at all concentrations (1; 10; 50 nM) and time tested (1-10 min). We demonstrated that 24 h of E, treatment markedly increased VSMC proliferation (53% above control), and this effect was suppressed by a PKC inhibitor. The rapid and the long term effects of the hormone were completely suppressed in the presence of an estradiol receptor antagonist (ICI 182780). In summary, we provided evidence that, the steroid exerts both non-genomic and genomic actions, the former associated with MAPK kinase dependent on NO production, and the latter related with induction of VSMC proliferation involving PKC pathway activation. (C) 2007 Elsevier Inc. All rights reserved.
机译：最近已经提出了类固醇作用的两步模型机制。在这项研究中，我们检验了以下假设：雌酮（E I）对血管组织的生化作用可以通过基因组和非基因组作用来执行。大鼠主动脉环或血管平滑肌细胞培养物（VSMC）用于测试激素对一氧化氮（NO）产生，蛋白激酶活性和细胞增殖的影响。我们的数据表明，雌酮可在30 s和20 min处理之间增加NO的合成，并且这种刺激作用取决于MAPK级联激活，因为在存在MAPK抑制剂（PD98059）时可以阻止它。使用磷酸化测定，我们还显示E显着增加MAPK活性。在浓度和时程研究中测量了激素对PKC活性的影响。用E直接处理大鼠主动脉匀浆，在所有浓度（1; 10; 50 nM）和测试时间（1-10分钟）下均显着增强PKC活性（增加1-10倍，p <0.01）。我们证明了E治疗24小时显着增加了VSMC增殖（比对照高53％），并且这种作用被PKC抑制剂所抑制。在雌二醇受体拮抗剂（ICI 182780）的存在下，激素的快速和长期作用被完全抑制。总之，我们提供的证据表明，类固醇发挥非基因组和基因组作用，前者与依赖于NO产生的MAPK激酶有关，而后者与涉及PKC途径活化的VSMC增殖的诱导有关。 （C）2007 Elsevier Inc.保留所有权利。

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