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使用GnRH激动剂阿扎那林作为可移除植入物“Gonazon”对犬内分泌和生精睾丸功能进行可逆性下调(激素去势):一项临床前试验

Reversible downregulation of endocrine and germinative testicular function (hormonal castration) in the dog with the GnRH-agonist azagly-nafarelin as a removable implant "Gonazon"; a preclinical trial.

作者信息

Ludwig C, Desmoulins P O, Driancourt M A, Goericke-Pesch S, Hoffmann B

机构信息

Klinik für Geburtshilfe, Gynäkologie und Andrologie der Gross- und Kleintiere, Justus-Liebig-Universität Giessen, Frankfurter Strasse 106, 35392 Giessen, Germany.

出版信息

Theriogenology. 2009 Apr 15;71(7):1037-45. doi: 10.1016/j.theriogenology.2008.10.015. Epub 2009 Feb 23.

DOI:10.1016/j.theriogenology.2008.10.015
PMID:19233456
Abstract

Downregulation of anterior pituitary GnRH-receptors by application of a slow release GnRH-implant offers an effective and reversible alternative to surgical castration of the male dog. Aim of the present study was to test the efficacy and the underlying mechanisms of a new non-biodegradable controlled-release device implant (Gonazon((R)), Intervet, containing 18.5mg of the GnRH-agonist Azagly-Nafarelin). Eight male beagle dogs were implanted s.c. at the para-umbilical region. In four dogs implant removal was after 180 days (group 1), in the other four dogs after 365 days (group 2). Eleven weeks after implantation availability of LH was reduced (p<0.0001) by 70%. After an initial increase lasting for about 4 days, testosterone (T) and estradiol (E2) concentrations decreased (p<0.0001) to basal levels within 17.5+/-8.4 days. Size of testes was decreased by about 82% after 17 weeks, size of prostate by about 46% after 5 weeks (p<0.0001). Five to 7 weeks after implantation all dogs were aspermic. Testosterone and estradiol concentrations, together with testicular and prostatic size remained suppressed in all dogs in group 1 and one dog of group 2 until implant removal. The other three dogs of group 2 escaped from down-regulation between 223 and 324 days. Effects on the availability of LH, T, E2 and on testicular and prostatic size were fully reversible after implant removal or escape from down-regulation. In six dogs semen quality was back to pre-treatment values after about 29 weeks, however, one dog developed oligozoospermia while another one stayed azoospermic, probably due to an obstruction within the epididymal duct.

摘要

通过植入缓释促性腺激素释放激素(GnRH)可使雄性犬垂体前叶GnRH受体下调,这为雄性犬去势提供了一种有效且可逆的替代手术去势的方法。本研究的目的是测试一种新型不可生物降解的控释装置植入物(Gonazon®,英特威,含18.5毫克GnRH激动剂阿扎甘萘法瑞林)的疗效及潜在机制。8只雄性比格犬在脐旁区域皮下植入该装置。4只犬在180天后取出植入物(第1组),另外4只犬在365天后取出(第2组)。植入后11周,促黄体生成素(LH)水平降低(p<0.0001)70%。在持续约4天的初始升高后,睾酮(T)和雌二醇(E2)浓度在17.5±8.4天内降至基础水平(p<0.0001)。17周后睾丸大小减少约82%,5周后前列腺大小减少约46%(p<0.0001)。植入后5至7周,所有犬均无精子。第1组所有犬及第2组的1只犬在取出植入物前,睾酮和雌二醇浓度以及睾丸和前列腺大小一直受到抑制。第2组的另外3只犬在223至324天之间摆脱了下调。取出植入物或摆脱下调后,对LH、T、E2水平以及睾丸和前列腺大小的影响完全可逆。6只犬的精液质量在约29周后恢复到治疗前水平,然而,1只犬出现少精子症,另1只犬持续无精子症,可能是由于附睾管阻塞。

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