Sliced testis assay prevalidation: Multichemical study
This study was designed to evaluate the sliced testis assay for the ability to screen chemicals with known mechanisms of action for anti-steroidogenic activity and/or for cytotoxicity. The 9 chemicals tested were aminoglutethimide (AG; positive control), 2,4-dinitrophenol (2,4-DNP; cytotoxicity control), flutamide, ketoconazole, vinclozolin, atrazine, dimethoate, finasteride, spironolactone, verapamil, and prochloraz. These chemicals, evaluated for anti-androgenic and/or cytotoxic effects in the in vitro sliced testis assay, produced the following results: Finasteride, a 5"-reductase inhibitor, prevents 5"-reductase from converting testosterone to dihydrotestosterone (DHT) in the testis and locally. DHT plays a major role in the perinatal determination of external male genitalia and structures of the lower male reproductive tract. In this assay, finasteride caused concentration-related decreases in testosterone levels; an opposite response of what was expected. Lactate dehydrogenase (LDH) levels were increased at 1000 :M finasteride, with no effects at 10 or 100 :M.