Effects of Deslorelin on Testosterone Secretion and Testicular Volume in Male Rhesus Macaques (Macaca mulatta).

Helena D Tran, Kelsey E Carroll, Alexis L Mackiewicz, Amir Ardeshir, Diane Stockinger, Thiago De Lucena, Kari L Christe
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Abstract

Sterility in male NHP has long been achieved through surgical castration or vasectomy. However, these techniques are irreversible, require a surgical procedure, and have potential consequences such as sperm granulomas and long recovery time. Deslorelin is a gonadotropin-releasing hormone agonist that temporarily and reversibly suppresses sex hormone secretion. Our goal in this study was to investigate the effects of deslorelin on testosterone secretion and testicular volume in male rhesus macaques (Macaca mulatta). Male macaques (n = 4) each received two, 4.7-mg deslorelin implants subcutaneously in the interscapular region. Serum testosterone and testicular volume were then monitored at specific time points until 10 mo after treatment. Testosterone suppression was defined as testosterone levels lower than 0.6 ng/mL for a sustained period of at least 30 d. After implantation, mean testicular volume was significantly reduced by day 121. Testosterone suppression was observed in all subjects. However, the time from implantation to testosterone suppression and duration of suppression varied. Two macaques were hormonally suppressed by day 26 after implantation and remained suppressed for at least 6 mo. The other 2 macaques were hormonally suppressed by 2 mo after implantation; of these two, one remained suppressed for 70 days while the other was suppressed for at least 245 days. We conclude that deslorelin can safely suppress testosterone secretion in male rhesus macaques, but individual variation in onset and duration of action should be considered when establishing reimplantation time points and potential return to reproductive activity.

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Deslorelin对雄性恒河猴睾酮分泌和睾丸体积的影响。
长期以来,男性NHP的不育是通过手术阉割或输精管切除术实现的。然而,这些技术是不可逆转的,需要外科手术,并有潜在的后果,如精子肉芽肿和长时间的恢复。Deslorelin是一种促性腺激素释放激素激动剂,可暂时可逆地抑制性激素分泌。本研究的目的是研究地氯林对雄性恒河猴睾酮分泌和睾丸体积的影响。雄性猕猴(n=4)分别接受两个4.7mg的deslorelin植入物,植入物位于肩胛间区域。然后在特定时间点监测血清睾酮和睾丸体积,直到治疗后10个月。睾酮抑制被定义为睾酮水平在至少30天的持续时间内低于0.6 ng/mL。植入后,到第121天,平均睾丸体积显著减少。所有受试者均观察到睾酮抑制。然而,从植入到睾酮抑制的时间和抑制的持续时间各不相同。2只猕猴在植入后第26天受到激素抑制,并保持至少6个月的抑制。另外2只猕猴植入后2个月受到激素抑制;其中一个被抑制了70天,另一个被至少抑制了245天。我们得出的结论是,地洛林可以安全地抑制雄性恒河猴的睾酮分泌,但在确定植入时间点和可能恢复生殖活动时,应考虑发病和作用持续时间的个体差异。
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