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 microM and dibutyltin at 74 microM inhibited aromatase activity in vitro but monobutyltin 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 microM. 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 microM. Consequently, TBT is a competitive inhibitor of human aromatase with a Ki approximately 300-fold the K(m(app)) value.
Cooke
Gerard M
GM
Department of Cellular and Molecular Medicine, Sir Frederick G. Banting Research Center, University of Ottawa, PL 2202D1 Tunney's Pasture, ON, K1A 0L2, Ottawa, Canada. gerard_cooke@hc-sc.gc.ca
D000818:Animals; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009947:Organotin Compounds / Q000494:pharmacology*; D013739:Testosterone / Q000378:metabolism
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009947:Organotin Compounds; D013739:Testosterone; D001141:Aromatase