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Androgen receptors in experimentally induced colon carcinogenesis

  • Original Papers
  • Experimental Oncology
  • Published:
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Summary

Sex hormones may play a role in colonic carcinogenesis, as evidenced by epidemiologic and experimental data showing different tumor rates in males and females. We investigated the effects of hormonal manipulation on tumor development and on androgen receptor binding in both colonic wall and experimentally induced tumors in male rats. Five of six groups, each with 40 animals, were given 10 weekly s.c. injections of azoxymethane (AOM), 7.5 mg/kg body weight. Group-I served as normal controls. Group-II received AOM only. Group-III was castrated 2 weeks prior to carcinogen treatment. Group-IV was castrated similarly and then hormone substituted with testosterone propionate. Group-V was chemically castrated with the anti androgen cyproterone acetate. Group-VI was castrated and given hormone vehicle. Scatchard analysis for androgen receptors in cytosol from normal colonic wall and tumor was performed with 3H-methyltrienolone as the ligand.

Androgens were found to have an inhibitory effect on carcinogenesis: chemical castration increased colonic tumor development (P<0.05 for multiplicity), and testosterone administration produced a borderline statistically significant reduction in tumor incidence in surgically castrated rats (P<0.053), particularly in the right colon. Specific binding sites for androgen with high affinity and low capacity were found in the colonic wall of all groups. Receptor density was not altered by AOM administration, but increased after surgical castration. Receptor density was markedly lower in tumors than in normal colonic wall. Receptor binding sites in tumors were not altered by the various hormonal manipulations.

Our study demonstrated that although cytoplasmic androgen receptors are present in colonic wall and in experimental tumors, AOM-induced colonic carcinogenesis appears to be only mildly affected by manipulation of androgens.

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Authors and Affiliations

  1. II. Department of Surgery, University of Cologne, D-5000, Köln 91, Federal Republic of Germany

    J. R. Izbicki, E. Harnisch, R. Hogenschurz, W. Izbicki & J. Kusche

  2. II. Department of Internal Medicine, University of Cologne, D-5000, Köln 91, Federal Republic of Germany

    G. Wambach

  3. Department of Pathology, The Johns Hopkins University, School of Medicine and Hospital, 21205, Baltimore, MD, USA

    S. R. Hamilton

  4. Department of Surgery, University of Munich, D-8000, München 2, Federal Republic of Germany

    J. R. Izbicki

Authors
  1. J. R. Izbicki
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  2. G. Wambach
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  3. S. R. Hamilton
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  4. E. Harnisch
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  5. R. Hogenschurz
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  6. W. Izbicki
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  7. J. Kusche
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Supported by a grant of the Deutsche Forschungsgemeinschaft Grant No. Iz 1/1-1, by the Ministry for Science and Research NRW, and by the Julia Baker Fund

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Izbicki, J.R., Wambach, G., Hamilton, S.R. et al. Androgen receptors in experimentally induced colon carcinogenesis. J Cancer Res Clin Oncol 112, 39–46 (1986). https://doi.org/10.1007/BF00394937

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  • DOI: https://doi.org/10.1007/BF00394937

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