Effects of bleomycin, etoposide and cisplatin treatment on Leydig cell structure and transcription of steroidogenic enzymes in rat testis

Cytotoxic anticancer chemotherapy affects pituitary-testicular hormonal axis in humans and in animals. This study investigated the effects on Leydig cells of three cycles of bleomycin, etoposide and cisplatin (0.75, 7.5, and 1.5 mg/kg, respectively; BEP) chemotherapy in rat testis. The chemotherapy has induced hyperplasia of and degenerative changes in Leydig cells at the end of BEP exposure, which remained so even after a recovery time of 63 days. The increased testicular oxidative stress at the end of the chemotherapy returned to normal level after the recovery time. The chemotherapy has stimulated the transcription of scavenger receptor class type-B1 (SCARB1), steroidogenic acute-regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), CYP17A1, and inhibited that of 17β-hydroxysteroid dehydrogenase (HSD17B6) and CYP19A1 in association with increased cholesterol and decreased testosterone levels. Even after the recovery time, the chemotherapy still had inhibitory effects on the transcription of all of the above genes in addition to luteinizing hormone receptor and HSD3B1, but not on the StAR gene. The cholesterol and testosterone levels also did not show any significant differences with the control group. The decreased testosterone level at the end of chemotherapy was probably due to inhibition of HSD3B1 and HSD17B6 genes. In conclusion, clinically relevant dose-levels and treatment protocols of BEP chemotherapy adversely affect Leydig cell function. The BEP chemotherapy inhibits the transcription of steroidogenic enzymes and that these effects sustain over an extended period of time without returning to normal levels.