Habenicht U F, Schneider M R, el Etreby M F
Research Laboratories of Schering AG, Berlin, Federal Republic of Germany.
Prostate. 1990;17(1):69-83. doi: 10.1002/pros.2990170108.
LHRH-antagonists might represent a useful new type of androgen deprivation to treat prostatic cancer. In this context adult intact male rats were treated subcutaneously with different concentrations of the new LHRH-antagonist antide either once (1, 3, 6, 10, 15 mg/kg) or on 5 consecutive days (5 x 3 mg/kg). The effect on serum concentration of LH and testosterone and the effect on the weights of testes, prostate, and seminal vesicles was investigated after different periods of time (24 hours, 1, 2, 3, 5, and 8 weeks). Histological evaluation of the testes was also performed. A clear dose-dependent inhibitory effect on the above-mentioned parameters was observed. The most effective treatment schedule was the single application of 15 mg/kg resulting in castration-like inhibition of prostate weights and marked inhibition of spermatogenesis within 2 weeks, which was maintained 8 weeks after the injection. Serum LH and serum testosterone concentrations were below the detection limit of the assay within 2 weeks and showed first signs of recovery after 8 weeks. Histologically, no signs indicative of irreversible effects (testes) were observed. To summarize, the LHRH-antagonist antide was found to have a profound long-lasting inhibitory but reversible effect on the reproductive system of adult intact male rats. These data emphasize the suitability of this type of compound for the treatment of prostatic cancer.
促黄体生成素释放激素（LHRH）拮抗剂可能是一种用于治疗前列腺癌的新型有效雄激素剥夺药物。在此背景下，成年未阉割雄性大鼠皮下注射不同浓度的新型LHRH拮抗剂安替肽，单次注射（1、3、6、10、15毫克/千克）或连续5天注射（5×3毫克/千克）。在不同时间段（24小时、1、2、3、5和8周）后，研究其对血清促黄体生成素（LH）和睾酮浓度的影响，以及对睾丸、前列腺和精囊重量的影响。同时也对睾丸进行了组织学评估。观察到对上述参数有明显的剂量依赖性抑制作用。最有效的治疗方案是单次注射15毫克/千克，可在2周内产生类似去势的前列腺重量抑制作用，并显著抑制精子发生，这种抑制作用在注射后8周仍持续存在。血清LH和血清睾酮浓度在2周内低于检测限，8周后开始出现恢复迹象。组织学检查未观察到不可逆影响（睾丸）的迹象。总之，发现LHRH拮抗剂安替肽对成年未阉割雄性大鼠的生殖系统具有深远的长期抑制但可逆的作用。这些数据强调了这类化合物用于治疗前列腺癌的适用性。
