The inhibitory effects of lead on steroidogenesis in MA-10 mouse Leydig tumor cells

Lead is an environmental and occupational pollutant. It has been reported t hat lead affects the male reproductive system in humans and animals. Howeve r, the cellular mechanism of the adverse effect of lead on Leydig cell ster oidogenesis remains unknown. To clarify whether lead has a direct effect on Leydig cells and how lead affects Leydig cells, MA-10 cells, a mouse Leydi g tumor cell line, were exploited in this study. Lead acetate significantly inhibited hCG- and dbcAMP-stimulated progesterone production in MA-10 cell s at 2 h. Steroid production stimulated by hCG or dbcAMP were reduced by le ad. The mechanism of lead in reducing MA-10 cell steroidogenesis was furthe r investigated. The expression of Steroidogenic Acute Regulatory (StAR) pro tein and the activities of P450 side-chain cleavage (P450scc) and SP-hydrox ysteroid dehydrogenase (3 beta -HSD) enzymes were detected. Cells were trea ted with dbcAMP, 22R-hydroxycholesterol or pregnenolone alone or in combina tion with lead acetate ranging from 10(-8) to 10(-5) M for 2 h. The express ion of StAR protein stimulated by dbcAMP was suppressed by lead at about 50 %. Progesterone productions treated with 22R-hydroxycholesterol or pregneno lone were reduced 30-40% in lead-treated MA-10 cells. These data suggest th at lead directly inhibited steroidogenesis by decreasing StAR protein expre ssion and the activities of P450scc and 3 beta -HSD enzymes with a dose-res ponse trend in MA-10 cells. Moreover, cadmium, a calcium channel blocker, a bolished inhibitory effect of lead on MA-10 cell steroid production. This i ndicates that lead might act on calcium channel to regulate MA-10 cell ster oidogenesis. (C) 2001 Elsevier Science Inc. All rights reserved.