Wang Zhong-Lin, Yang Ling-Yu, Chen Hong-Huan, Lin Hsiao-Hsin, Tsai Yi-Ting, Huang William J
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Department of Pediatrics, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
PLoS One. 2017 Aug 1;12(8):e0181952. doi: 10.1371/journal.pone.0181952. eCollection 2017.
This study aimed to investigate the effects of anti-tumor necrosis factor (TNF)-α antibody (Ab) on alteration of penile structure in the hyperprolactinemia (hyperPRL) rat model. HyperPRL was induced in 8-week-old male Sprague-Dawley rats by allografting anterior pituitary (AP) glands under the renal capsule (+AP rats). Rats implanted with cerebral cortex (CX) were used as sham control (+CX rats). At 6 weeks post implantation, rats received either a single intra-testicular dose of TNF-α Ab (12.5 μg/kg) or testosterone replacement (2 doses of testosterone enanthate [TE], 3 mg/kg), and they were sacrificed 1 week later. Blood and penile tissue was collected for analysis. Compared to +CX rats, the +AP group had lower serum testosterone concentration and neuronal nitric oxide synthase (nNOS) expression, but exhibited a higher ratio of collagen III/I in the corpus cavernosum. Smooth muscle content exhibited no significant changes. At 1 week post TNF-α Ab injection, the collagen III/I ratio in the +AP group was decreased, and the smooth muscle content and nNOS expression increased significantly. These findings were comparable to those observed in +AP rats receiving TE. Testicular TNF-α suppresses testosterone release, which in turn results in the erectile dysfunction (ED) seen in hyperPRL. Intra-testicular TNF-α Ab treatment is as effective as testosterone supplementation on penile structure normalization in the hyperPRL model.
本研究旨在探讨抗肿瘤坏死因子（TNF）-α抗体（Ab）对高泌乳素血症（高PRL）大鼠模型阴茎结构改变的影响。通过将垂体前叶（AP）移植到8周龄雄性Sprague-Dawley大鼠肾包膜下诱导高PRL血症（+AP大鼠）。植入大脑皮质（CX）的大鼠用作假手术对照（+CX大鼠）。植入后6周，大鼠接受单次睾丸内注射TNF-α Ab（12.5μg/kg）或睾酮替代治疗（2剂庚酸睾酮[TE]，3mg/kg），1周后处死。收集血液和阴茎组织进行分析。与+CX大鼠相比，+AP组血清睾酮浓度和神经元型一氧化氮合酶（nNOS）表达较低，但海绵体中III型/ I型胶原蛋白比例较高。平滑肌含量无显著变化。注射TNF-α Ab后1周，+AP组的III型/ I型胶原蛋白比例降低，平滑肌含量和nNOS表达显著增加。这些发现与接受TE的+AP大鼠中观察到的结果相当。睾丸TNF-α抑制睾酮释放，进而导致高PRL血症中出现的勃起功能障碍（ED）。在高PRL模型中，睾丸内注射TNF-α Ab治疗在阴茎结构正常化方面与补充睾酮一样有效。
