Effects of TNF-α on penile structure alteration in rats with hyperprolactinemia

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.本研究旨在探究抗肿瘤坏死因子(TNF)-α抗体(Ab)对高泌乳素血症(hyperPRL)大鼠模型阴茎结构改变的影响。研究通过在8周龄雄性斯普拉格-道利大鼠肾包膜下移植垂体前叶(AP)腺体，构建高泌乳素血症模型（下称+AP组大鼠）；以接受大脑皮层(CX)移植的大鼠作为假手术对照（下称+CX组大鼠）。移植术后6周，大鼠分别接受单次睾丸内注射抗肿瘤坏死因子-α抗体（剂量为12.5 μg/kg），或睾酮替代治疗（庚酸睾酮(TE)，3 mg/kg，共给药2次），并于给药1周后处死取材。随后收集血液与阴茎组织用于后续检测分析。与+CX组大鼠相比，+AP组大鼠血清睾酮浓度与神经元型一氧化氮合酶(nNOS)表达水平均更低，但阴茎海绵体的Ⅲ型胶原/Ⅰ型胶原比值更高；平滑肌含量无显著变化。抗肿瘤坏死因子-α抗体注射1周后，+AP组大鼠的Ⅲ型胶原/Ⅰ型胶原比值降低，平滑肌含量与nNOS表达水平均显著升高，该改善效果与接受庚酸睾酮治疗的+AP组大鼠观测结果一致。研究表明，睾丸源性肿瘤坏死因子-α可抑制睾酮释放，进而引发高泌乳素血症相关勃起功能障碍(ED)；在高泌乳素血症模型中，睾丸内注射抗肿瘤坏死因子-α抗体治疗在阴茎结构恢复正常方面，效果与睾酮补充治疗相当。