Modulation of the testicular steroidogenic pathway by cyclosporin A in adult rats pretreated with diethylstilbestrol.

Treatment of male Fischer-344 rats with diethylstilbestrol (DES) induces hyperprolactinemia and alterations in testicular steroidogenesis. Cyclosporin A (CsA), an immunosuppressive drug, is believed to act by opposing the effects of prolactin (PRL) and was reported to influence testicular function. We have examined the effect of CsA on gonadal function in rats pre-treated with DES. Male rats were implanted with DES-containing silastic capsules. After 19 weeks, the capsules were removed, and, starting 2.5 weeks later, rats were treated for 1 week with CsA. At sacrifice, plasma and testes were collected. Testis fragments were incubated with or without 12.5 mlU of human chorionic gonadotropin (hCG)/ml at 32 degrees C for 4 hr. As expected, plasma PRL levels were increased in DES exposed rats, while testicular, seminal vesicle, and prostate weights were reduced. Cyclosporin A treatment did not further modify these parameters. Treatment with CsA and/or DES decreased circulating levels of testosterone, while testosterone content in the testes was not modified. Although CsA did not affect in vitro release of testosterone, it reduced the stimulatory influence of DES pretreatment on testicular responses to hCG in vitro. Plasma and testicular content of progesterone (P) was increased by DES administration but was not affected by CsA. Both CsA and DES administration decreased plasma 17-OH-Progesterone (17-OH-P) levels, but only CsA decreased testicular 17-OH-P contents. Combined exposure to CsA and DES enhanced the stimulatory effect of hCG on the accumulation of 17-OH-P in the media. Media estradiol levels were not affected by treatment with either CsA or DES. The present results indicate that CsA may interfere with the enhancement of the conversion of P to testosterone in DES-treated rats. As CsA did not change plasma PRL or gonadotropin levels, a direct effect of the drug on the testicular function is suspected.