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首页> 外文期刊>Reproductive toxicology >Testicular toxicity induced by a triple neurokinin receptor antagonist in male dogs.
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Testicular toxicity induced by a triple neurokinin receptor antagonist in male dogs.

机译：三重神经激肽受体拮抗剂在雄性狗中引起的睾丸毒性。

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Mechanism mediating the testicular toxicity induced by CS-003, a triple neurokinin receptor antagonist, was investigated in male dogs. Daily CS-003 administrations showed testicular toxicity, such as a decrease in the sperm number, motility and prostate weight; and an increase in sperm abnormality, accompanying histopathological changes in the testis, epididymis and prostate. A single CS-003 administration suppressed plasma testosterone and LH levels in intact and castrated males. The suppressed LH release was restored by GnRH agonist injection, suggesting that pituitary sensitivity to GnRH is not impaired by CS-003. Treatment with SB223412, a neurokinin 3 receptor antagonist, caused a similar effect to CS-003, such as toxicity in the testis, prostate and epididymis and decreased plasma level of LH and testosterone. In conclusion, CS-003-induced testicular toxicity is caused by the inhibition of neurokinin Beurokinin 3 receptor signaling probably at the hypothalamic level in male dogs.
机译：在雄性狗中研究了介导由三重神经激肽受体拮抗剂CS-003诱导的睾丸毒性的机制。每日CS-003给药显示睾丸毒性，例如精子数量，运动性和前列腺重量减少;精子异常的增加，伴随着睾丸，附睾和前列腺的组织病理学变化。一次CS-003给药可抑制完整和去势男性的血浆睾丸激素和LH水平。通过GnRH激动剂注射恢复了抑制的LH释放，这表明CS-003不会损害垂体对GnRH的敏感性。用神经激肽3受体拮抗剂SB223412进行治疗，可产生与CS-003类似的作用，例如对睾丸，前列腺和附睾有毒性，并降低LH和睾丸激素的血浆水平。总之，CS-003诱导的睾丸毒性是由雄性狗的下丘脑水平抑制神经激肽B /神经激肽3受体信号传导引起的。

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