Effect of tamoxifen on spermatogenesis and testicular steroidogenesis

The aim of this study was to evaluate the effects of in vivo and in vitro treatments with selective estrogen receptor modulator (SERM), tamoxifen on testicular functions. The testis treated with tamoxifen, in vivo or in vitro, showed dose-dependent regressive changes in spermatogenesis. This study showed that the decreased estrogenic effect due to tamoxifen may be directly responsible for decreased testicular expression of aromatase, which in turn may be responsible for decreased synthesis of estradiol in the testis. The decreased endogenous estradiol through cAMP-CREB signaling mechanism may decline germ cells proliferation (PCNA) and survival (Bcl2). The tamoxifen-induced decreased estrogenic effect may also be responsible for increased expression of testicular NOS and consequently increased production of NO, which may cause increased germ cells apoptosis (Caspase-3) and impaired spermatogenesis. Both in vivo and in vitro studies showed the inhibitory effect on testicular steroidogenic factors. Thus, tamoxifen inhibits testicular spermatogenesis and steroidogenesis either directly acting on testis or indirectly through gonadotropin release.