Cátedra de Bioquímica Clínica II, Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, San Juan 670, B8000ICN Bahía Blanca, Argentina.
Steroids. 2012 Sep;77(11):1033-40. doi: 10.1016/j.steroids.2012.05.008. Epub 2012 Jun 20.
In this work we investigated the role of testosterone on cellular processes involved in vascular disease, and whether these effects depend on its local conversion to estradiol. Cultures of rat aortic endothelial and smooth muscle cells in vitro treated with physiological concentrations of testosterone were employed. Testosterone rapidly increased endothelial nitric oxide production. To evaluate whether this non genomic action was dependent on testosterone aromatization we used an aromatase inhibitor. Anastrozole compound did not modify the fast increase in nitric oxide production elicited by testosterone. The hormonal effect was completely blocked by an androgen receptor antagonist (flutamide); meanwhile it wasn't modified by the presence of an estrogen receptor antagonist (ICI182780).The possibility of intracellular estradiol synthesis was ruled out when no differences were found in estradiol measurements performed in culture incubation medium from control and testosterone treated cells. The 5α-reductase inhibitor finasteride partially suppressed the enhancement in nitric oxide production, suggesting that the effect of testosterone was partially due to dihydrotestosterone conversion. Testosterone stimulated muscle cell proliferation independent of local conversion to estradiol. When cellular events that play key roles in vascular disease development were analyzed, testosterone prevented monocyte adhesion to endothelial cells induced by a proinflammatory stimulus (bacterial lipopolysaccharides), and prompted muscle cell migration in presence of a cell motility inducer. In summary, testosterone modulates vascular behavior through its direct action on vascular cells independent of aromatization to estradiol. The cellular actions exhibited by the steroid varied whether cells were under basal or inflammatory conditions.
在这项工作中，我们研究了睾酮在血管疾病相关细胞过程中的作用，以及这些作用是否依赖于其局部转化为雌二醇。我们在体外培养了大鼠主动脉内皮和平滑肌细胞，并用生理浓度的睾酮处理这些细胞。睾酮可迅速增加内皮细胞一氧化氮的产生。为了评估这种非基因组作用是否依赖于睾酮的芳香化作用，我们使用了一种芳香酶抑制剂。阿那曲唑化合物并不能改变睾酮引起的一氧化氮产生的快速增加。该激素作用被雄激素受体拮抗剂（氟他胺）完全阻断；而雌激素受体拮抗剂（ICI182780）并不改变该作用。当在对照和睾酮处理的细胞的培养孵育培养基中进行的雌二醇测量中未发现差异时，排除了细胞内合成雌二醇的可能性。5α-还原酶抑制剂非那雄胺部分抑制了一氧化氮产生的增强，表明睾酮的作用部分归因于二氢睾酮的转化。睾酮可刺激肌肉细胞增殖，而与局部转化为雌二醇无关。当分析在血管疾病发展中起关键作用的细胞事件时，发现睾酮可防止单核细胞在内皮细胞上的粘附，该粘附由促炎刺激（细菌脂多糖）诱导；并且在存在细胞运动诱导剂的情况下刺激肌肉细胞迁移。总之，睾酮通过其对血管细胞的直接作用来调节血管行为，而无需转化为雌二醇。在基础或炎症条件下，类固醇的细胞作用不同。
