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

  • Erika Pfeiffer
  • Manfred Metzler


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.


Covalent Binding Steroidal Estrogen Peroxidative Oxidation Free Sulfhydryl Group Catechol Estrogen 
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  1. 1.
    Tsutsui T, Maizumi H, McLachlan JA, Barrett JC (1983) Aneuploidy induction and cell transformation by diethylstilbestrol: a possible chromosomal mechanism in carcinogenesis. Cancer Res 43: 3814–3821.PubMedGoogle Scholar
  2. 2.
    Tsutsui T, Suzuki N, Fukuda S, Sato M, Maizumi H, McLachlan JA, Barrett JC (1987) 17ß-Estradiol-induced cell transformation and aneuploidy of Syrian hamster embryo cells in culture. Carcinogenesis 8: 1715–1719.Google Scholar
  3. 3.
    Epe B, Hegler J, Metzler M (1987) Site-specific covalent binding of stilbene-type and steroidal estrogens to tubulin following metabolic activation in vitro. Carcinogenesis 8: 1271–1275.PubMedCrossRefGoogle Scholar
  4. 4.
    Epe B, Harttig UH, Schiffmann D, Metzler M (1989) Microtubular proteins as cellular targets for carcinogenic estrogens and other carcinogens. In: Mechanisms of Chromosome Distribution and Aneuploidy (Resnick MA; Vig BK, Eds) Allan R Liss Inc, New York 1989, pp 345351.Google Scholar
  5. 5.
    Epe B, Harttig U, Stopper H, Metzler M (1990) Covalent binding of reactive estrogen metabolites to microtubular protein as a possible mechanism of aneuploidy induction and neoplastic cell transformation. Environ Health Perspect 88: 123–127.PubMedGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • Erika Pfeiffer
  • Manfred Metzler

There are no affiliations available

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