Concentration dependency in lead-inhibited steroidogenesis in MA-10 mouse Leydig tumor cells.

Lead acetate (Pb) decreases the expression of steroidogenic acute regulatory (StAR) protein and the enzymatic activities of cytochrome P-450 side-chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in a concentration-dependent manner in Leydig cells at 2 h, the duration of submaximal inhibition. This study was undertaken at 3 h of Pb incubation to compare the effects at maximal metal inhibition of steroidogenesis. Quantitatively a 3-h Pb incubation with MA-10 cells resulted in higher decreases in human chorionic gonadotropin (hCG)-stimulated progesterone production, expression of StAR protein, and the activity of 3beta-HSD compared to 2 h. In contrast, lead inhibited dibutyryl cAMP (dbcAMP)-stimulated progesterone production but lacked this effect at 2 h. Surprisingly, Pb at 3 h of incubation did not affect P450scc enzyme activity, yet this enzymatic activity was inhibited at 2 h. Data indicate that incubation time is a factor in Pb-induced alterations in MA- 10 cell steroidogenesis.