Verma R, Krishna A. Effect of tamoxifen on spermatogenesis and testicular steroidogenesis. Biochem Biophys Res Commun 2017;486(1):36-42. http://www.sciencedirect.com/science/article/pii/S0006291X17303832
Highlights
· Treatment of tamoxifen, in vivo or in vitro, caused dose-dependent regressive changes in spermatogenesis.
· The tamoxifen induced decreased estradiol suppresses germ cells proliferation and survival via cAMP-CREB signaling.
· The tamoxifen-induced decreased estrogen may increase production of NO by increasing expression of iNOS.
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.
