Effects of Steroidal and Stilbene Estrogens and Their Peroxidative Metabolites on Microtubular Proteins

  • Erika Pfeiffer
  • Manfred Metzler
Conference paper

Summary

In order to elucidate the biochemical mechanisms of estrogen-induced aneuploidy and to evaluate the role of peroxidase-mediated activation, we have studied the interaction of microtubular proteins (MTP) and the inhibitory effect on microtubule (MT) assembly in a cell-free system of various steroidal and stilbene estrogens and their peroxidative metabolites. Steroidal estrogens, e.g., estrone and estradiol, and their catechol 2- and 4-hydroxy derivatives, neither bound to MTP nor inhibited MT assembly. However, the catechol estrogens exhibited strong binding and inhibition after peroxidase-mediated activation. Binding reduced the number of free sulfhydryl groups (by one at 50% inhibition) compared with control MTP and so involved the MTP cysteines. Addition of cysteine before MTP prevented both binding and inhibition. Some stilbene estrogens, e.g., diethylstilbestrol and E,E-dienestrol, inhibited MT polymerization directly, whereas others, e.g., indenestrol A, needed peroxidative activation. Therefore, peroxidase-mediated metabolism appears to play a role in MTP interaction for some but not all estrogens.

Keywords

Hydrogen Peroxide Estrogen Titration Cysteine Adduct 

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References

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Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • Erika Pfeiffer
  • Manfred Metzler

There are no affiliations available

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