Inhibition of rat testis microsomal 3β-hydroxysteroid dehydrogenase activity by tributyltin

In this study, we have examined the effects of a range of organotin compounds (mono-, di-, tributyltin, mono-, di-, trioctyltin) on the activities of rat testis microsomal 3beta-hydroxysteroid dehydrogenase (3beta-HSD), 17-hydroxylase (17-OHase) and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). 17-OHase activity was inhibited by more than 50% compared with the control rate by 59 muM tributyltin (TBT) but other organotin compounds showed no inhibition. 17beta-HSD activity was unaffected by all organotins tested. 3beta-HSD was inhibited by monooctyltin (81 muM) and by TBT at all concentrations tested in a dose-dependent manner, with almost complete loss of activity at TBT concentrations of 12 muM. The mechanism of inhibition of 3beta-HSD was investigated in kinetic analysis with 0-12 muM TBT. Three rat testis microsomal preparations were incubated with dehydroepiandrosterone as the steroid substrate ranging from 1 to 10,000 nM. Tributyltin was primarily a competitive inhibitor of 3beta-HSD activity, causing an increase in the value of the K-m(app). However, the mechanism was not entirely competitive as while there was an increase in K-m(app), a decrease in the V-max(app) was also observed with increasing concentrations of TBT. Slope and intercept replots demonstrated that the K-i(app) from slope replots was around 2.7 muM whereas the K-i(app) value from intercept replots was around 30 muM. When compared with the K-m(app) for 3beta-HSD of around 0.42 muM, TBT could be an effective inhibitor of this enzyme. Crown Copyright (C) 2003 Published by Elsevier Ltd. All rights reserved.