Dibutyltin (DBT) inhibits in vitro androgen biosynthesis of rat immature Leydig cells

Dibutyltin (DBT) is an organotine widely applied in stabilizing plastics and de-worm poultry agents. But the effects of DBT on immature Leydig cells remain elusive. Thus, the present study aims to investigate whether in vitro exposure to DBT affects immature Leydig cell function of androgen production and delineate the underlying mechanisms. 35 days old rat immature Leydig cells were isolated and exposed to DBT at different concentrations (0, 0.1, 0.5, and 1 μM). It was found that 0.5 and 1 μM DBT lowered androgen production from immature Leydig cells under basal conditions. DBT at 1 μM lowered androgen production from immature Leydig cells under the stimulations from luteinizing hormone or 8-Br-cAMP. DBT at 1 μM lowered 22R-hydroxycholesterol and pregnenolone-mediated androgen production from immature Leydig cells. DBT at 0.1, 0.5, and 1 μM down-regulated the mRNA expression levels of Lhcgr, Star, Cyp11a1, Hsd3b1, and Nr5a1. Further investigation found that DBT at 1 μM directly inhibited CYP11A1 and 3β-HSD1 enzyme activities. In conclusion, this study told us that in vitro exposure to DBT inhibited androgen biosynthesis in immature Leydig cells by selectively interfering with the expressions and enzyme activities of CYP11A1 and 3β-HSD1.