Sinha-Hikim A P, Swerdloff R S
Division of Endocrinology, Harbor-UCLA Medical Center, Torrance 90509.
Endocrinology. 1993 Nov;133(5):2161-70. doi: 10.1210/endo.133.5.8404667.
GnRH antagonists (GnRH-As) rapidly and reversibly inhibit testicular functions in a variety of experimental models as well as man. Their potential for human male contraception is currently being tested in many centers, including our own. This study was undertaken to provide comprehensive quantitative information on the testes and to document the temporal and stage-specific changes in the kinetics of germ cell degeneration in rats treated daily with the Nal-Glu GnRH-A (1250 micrograms/kg body wt) for up to 4 weeks. Plasma levels of testosterone (T) and the concentrations of testicular T declined to 20.7% and 5.4% of control values, respectively, by 1 week and remained suppressed throughout the treatment period. Preleptotene and pachytene spermatocytes, and step-7 and step-19 spermatids at stage VII were the first germ cells to degenerate soon after (1 week) GnRH-A treatment. Germ cell counts at stage VII also revealed a significant (P < 0.05) reduction in number of preleptotene (25.6%), pachytene (35.4%), and step-7 spermatids (29.1%) in comparison with controls. The number of homogenization-resistant advanced spermatids decreased by 70%. A further progressive loss of spermatogenic activity occurred with time. Treatment with GnRH-A for 4 weeks caused advanced spermatids to decline to nearly undetectable, Step-7 spermatids to decline to 17.7% of the normal level, and the P and PL to decline to 28.6% and 67.7%, respectively, of control values. The number of Sertoli cells and A1 spermatogonia remained unchanged throughout the experimental period. The effects of GnRH-A treatment on spermatogenesis were identical to that of hypophysectomy. These results suggest that: 1) early deprivation of gonadotropins and/or intratesticular T by GnRH-A treatment is followed by stage-specific degeneration of germ cells; 2) pituitary secretions other than LH and FSH have little primary influence on spermatogenesis during early regression; and 3) the GnRH-A-treated rat would be an excellent animal model for studying the targeted effects of LH, FSH, and T on the regulation of spermatogenesis.
促性腺激素释放激素拮抗剂（GnRH-As）在多种实验模型以及人类中能迅速且可逆地抑制睾丸功能。目前，包括我们中心在内的许多机构正在测试其用于人类男性避孕的潜力。本研究旨在提供关于睾丸的全面定量信息，并记录每日用那格列奈-谷氨酸GnRH-A（1250微克/千克体重）处理长达4周的大鼠生殖细胞变性动力学的时间和阶段特异性变化。睾酮（T）的血浆水平和睾丸T的浓度在1周时分别降至对照值的20.7%和5.4%，并在整个治疗期间一直受到抑制。细线前期和粗线期精母细胞以及VII期的7步和19步精子细胞是GnRH-A处理后（1周）最早发生变性的生殖细胞。VII期的生殖细胞计数还显示，与对照组相比，细线前期（25.6%）、粗线期（35.4%）和7步精子细胞（29.1%）的数量显著减少（P < 0.05）。抗均质化晚期精子细胞的数量减少了70%。随着时间的推移，生精活性进一步逐渐丧失。用GnRH-A处理4周导致晚期精子细胞降至几乎无法检测到的水平，7步精子细胞降至正常水平的17.7%，P期和PL期分别降至对照值的28.6%和67.7%。在整个实验期间，支持细胞和A1精原细胞的数量保持不变。GnRH-A处理对精子发生的影响与垂体切除相同。这些结果表明：1）GnRH-A处理早期导致促性腺激素和/或睾丸内T缺乏，随后生殖细胞发生阶段特异性变性；2）在早期退化过程中，除LH和FSH外的垂体分泌物对精子发生几乎没有主要影响；3）GnRH-A处理的大鼠将是研究LH、FSH和T对精子发生调节的靶向作用的优秀动物模型。
