Effect of organotins on human aromatase activity in vitro

The interaction between the human aromatase enzyme and some organotins was investigated. Tributyltin (TBT) at 12 and 59 muM and dibutyltin ast 74 muM inhibited aromatase activity in vitro but inonobutyltin and tri-, di- and monooctyltins were without effect. In four separate kinetic studies of aromatase, the K-m(app) for testosterone was 0.24, 0,21, 0.16 and 0.24 AM, TBT inhibited aromatase activity by causing the K-m(app) to be increased without affecting the V-max indicative of competitive inhibition. Slope and intercept replots confirmed the effect of aromatase on the K-m(app) Slope replots from three separate kinetic studies provided Ki values for TBT of 64.5, 40.9 and 37.3 muM. Consequently, TBT is a competitive inhibitor of human aromatase with a Ki approximately 300-fold the K-m(app) value. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.