Quintar A A, Leimgruber C, Pessah O A, Doll A, Maldonado C A
Centro de Microscopía Electrónica, INICSA-CONICET.
Cátedra de Bacteriología y Virología Médicas, Facultad de Ciencias Médicas, Universidad Nacional de Córdoba, X5000HRA, Córdoba, Argentina.
Int J Androl. 2012 Dec;35(6):845-859. doi: 10.1111/j.1365-2605.2012.01288.x. Epub 2012 Jun 19.
The defence of the male reproductive tract against microorganisms is critical for fertilization. The prostate gland has been reported to express several molecules of the innate immune system. However, little information is available about how androgens may modulate host defences within the prostate. We therefore aimed to examine in the rat the expression of the TLR4 system, which is strongly involved in pathogen recognition, and the secretion of the antibacterial substances rBD-1 and SP-D after androgen withdrawal. Immunoblotting and immunocytochemical analysis revealed a time-dependent increase in these molecules after orchiectomy, with epithelial and stromal cells being an important source of prostatic host defence proteins. In view of this, we evaluated the potential improvement in antibacterial ability of the prostatic fluid from orchiectomized animals ex vivo. Only samples from rats at 5 days post-orchiectomy showed a slight inhibition of Escherichia coli growth. Finally, E. coli was inoculated into the ventral prostate of orchiectomized or control rats, with bacterial growth being counted at 5 days after infection. Animals with androgen depletion presented a lower bacterial count, and showed few histological signs of prostatic inflammation compared with controls. In vitro studies confirmed that isolated lipopolysaccharide (LPS)-treated prostatic cells in the absence of testosterone increased SP-D. Moreover, media from these cells showed a higher antimicrobial activity than supernatants from testosterone- and LPS-treated cells. Our findings indicate that testosterone maintains a reduced expression of key elements for innate immunity and diminishes the antibacterial ability of the rat prostate. These data may represent an important mechanism underlying the immunosuppressive activity of testosterone in the gland. However, this immunosuppressive function of androgens is understandable as a means of avoiding uncontrolled immune responses against the haploid male gamete in the reproductive tract.
男性生殖道对微生物的防御对于受精至关重要。据报道，前列腺可表达几种先天免疫系统分子。然而，关于雄激素如何调节前列腺内的宿主防御，目前所知甚少。因此，我们旨在研究大鼠体内雄激素去除后，强烈参与病原体识别的TLR4系统的表达以及抗菌物质rBD-1和SP-D的分泌情况。免疫印迹和免疫细胞化学分析显示，去势后这些分子呈时间依赖性增加，上皮细胞和基质细胞是前列腺宿主防御蛋白的重要来源。鉴于此，我们在体外评估了去势动物前列腺液抗菌能力的潜在改善情况。只有去势后5天的大鼠样本对大肠杆菌生长有轻微抑制作用。最后，将大肠杆菌接种到去势或对照大鼠的腹侧前列腺中，在感染后5天对细菌生长进行计数。与对照组相比，雄激素缺乏的动物细菌计数较低，且前列腺炎症的组织学迹象较少。体外研究证实，在无睾酮的情况下，分离的脂多糖（LPS）处理的前列腺细胞中SP-D增加。此外，这些细胞的培养基比睾酮和LPS处理的细胞的上清液具有更高的抗菌活性。我们的研究结果表明，睾酮维持先天免疫关键元件的低表达，并降低大鼠前列腺的抗菌能力。这些数据可能代表了睾酮在该腺体中免疫抑制活性的重要机制。然而，雄激素的这种免疫抑制功能可以理解为是一种避免对生殖道中单倍体雄配子产生不受控制的免疫反应的方式。
