Seethalakshmi L, Flores C, Carboni A A, Menon M
Division of Urologic, Transplantation and Surgery, University of Massachusetts Medical Center, Worcester 01655.
J Androl. 1990 Nov-Dec;11(6):491-7.
The authors had previously shown that the subcutaneous administration of cyclosporine (CsA) resulted in an impairment of spermatogenesis. Testosterone levels declined and gonadotropin levels increased, suggesting that CsA primarily affects the synthesis and secretion of testosterone. In this study, the authors attempted to determine whether the exogenous administration of testosterone would maintain spermatogenesis in animals treated with a very high dose of CsA. Sexually mature, male Sprague-Dawley rats were treated subcutaneously with CsA (40 mg/kg per day) alone, or in combination with testosterone propionate (TP; 2 and 5 mg/d per rat), for 14 days. As expected, CsA reduced the body and reproductive organ weights and the levels of serum testosterone, while elevating the levels of follicles-stimulating hormone (FSH) and luteinizing hormone (LH). Quantitative analysis of spermatogenesis revealed a decline in all the different types of germ cells in tubules at stage VII of the cycle of the seminiferous epithelium. Administration of TP in 2 and 5 mg/d per rat doses restored the body and reproductive organ weights and the circulating levels of FSH. The serum levels of LH were below the assay's minimum level of detectability. Analysis of spermatogenesis revealed a dose-dependent increase in the germ cell counts after the administration of 2 and 5 mg of TP. The circulating levels of CsA were also significantly reduced after TP administration. These results revealed that CsA-induced alteration in spermatogenesis can be prevented by the exogenous administration of testosterone.
作者们之前已表明，皮下注射环孢素（CsA）会导致精子发生受损。睾酮水平下降，促性腺激素水平升高，这表明CsA主要影响睾酮的合成和分泌。在本研究中，作者们试图确定外源性给予睾酮是否能维持用非常高剂量CsA处理的动物的精子发生。性成熟的雄性Sprague-Dawley大鼠皮下单独注射CsA（每天40 mg/kg），或与丙酸睾酮（TP；每只大鼠2和5 mg/d）联合注射，持续14天。正如预期的那样，CsA降低了体重和生殖器官重量以及血清睾酮水平，同时提高了促卵泡激素（FSH）和黄体生成素（LH）水平。精子发生的定量分析显示，在生精上皮周期第VII阶段的小管中，所有不同类型的生殖细胞数量均下降。以每只大鼠2和5 mg/d的剂量给予TP可恢复体重和生殖器官重量以及FSH的循环水平。LH的血清水平低于该检测方法的最低可检测水平。精子发生分析显示，给予2和5 mg TP后，生殖细胞数量呈剂量依赖性增加。给予TP后，CsA的循环水平也显著降低。这些结果表明，外源性给予睾酮可预防CsA诱导的精子发生改变。
