Triphenyltin and Tributyltin inhibit pig testicular 17β-hydroxysteroid dehydrogenase activity and suppress testicular testosterone biosynthesis

We previously reported that tributyltin chloride (TBT) and triphenyltin chloride (TPT) powerfully suppressed human chorionic gonadotropinand 8-bromo-cAMP-stimulated testosterone production in pig Leydig cells at concentrations that were not cytotoxic [Nakajima Y, Sato Q, Ohno S, Nakajin S. Organotin compounds suppress testosterone production in Leydig cells from neonatal pig testes. J Health Sci 2003;49:514-9]. This study investigated the effects of these organotin compounds on the activity of enzymes involved in testosterone biosynthesis in pig testis. At relatively low concentrations of,TPT, 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD; IC50 = 2.6 mu M) and cytochrome P450 17 alpha-hydroxylase/C17-20 lyase (IC50 = 117 mu M) activities were inhibited, whereas cholesterol side-chain cleavage cytochrome P450 and 3 beta-HSD/Delta(4)-Delta(5) isomerase activities were less sensitive. Overall, TPT was more effective than TBT. TPT also inhibited both ferredoxin reductase and P450 reductase activities at concentrations over 30 mu M; however, TBT had no effect, even at 100 mu M. The IC50 values of TPT were estimated to be 25.7 and 22.8 mu M for ferredoxin reductase and P450 reductase, respectively. The inhibitory effect of TPT (30 mu M) on microsomal 17 beta-HSD activity from pig testis was eliminated by pretreatment with the reducing agents dithiothreitol (1 mM) and dithioerythritol (1 mM). On the other hand, TPT (0.03 mu M) or TBT (0.1 mu M) exposure suppressed the testosterone production from androstenedione in pig Leydig cells indicating that these organotins inhibit 17 beta-HSD activity in vivo as well as in vitro, and the IC50 values of TPT and TBT for 17 beta-HSD activity were estimated to be 48 and 114 nM, respectively. Based on these results, it appears possible that the effects of TBT and TPT are largely due to direct inhibition of 17 beta-HSD activity in vivo. (c) 2005 Elsevier Inc. All rights reserved.