Tributyltin chloride suppresses the P450cl7 transcription involved in testosterone production induced by gonadotropin stimulation in cultured pig Leydig cells.

We previously reported that organotin compounds, such as tributyltin chloride (TBT), dibutyltin dichloride and triphenyltin chloride, strongly suppressed the testosterone production level in isolated neonatal pig testicular Leydig cells at a concentration without cytotoxicity. In this report, the action mechanisms of suppressive effect of the testosterone production by TBT were investigated. TBT (0.1μM) exposure to pig Leydig cells for 4h significantly decreased the intracellular cAMP level stimulated by human chorionic gonadotropin (hCG; 10IU/ml) and also the level stimulated by forskolin (25μM). In the same way, TBT exposure for 6 and 24h significantly decreased the 17α-hydroxylase/17,20-lyase (P450cl7) mRNA level stimulated by hCG. However, TBT exposure did not affect the mRNA levels of other steroidogenic enzymes, such as cholesterol side chain cleavage enzyme, 3β-hydroxysteroid dehydrogenase/Δ(4)-Δ(5) isomerase, 17β-hydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein, estimated by RT-PCR. These results suggest that TBT exposure inhibits the adenyl cyclase activity of Leydig cells, which in turn suppresses testosterone production due to a decrease in the P450cl7 transcription level induced by decreasing intracellular cAMP levels.