Hormonal Regulation of Hepatic Cell Proliferation and Apoptosis: Implications for Carcinogenesis

  • Rolf Schulte-Hermann
  • W. Bursch
  • B. Grasl-Kraupp
  • L. Müllauer
  • H. Ochs
  • W. Parzefall
  • B. Ruttkay-Nedecky
Conference paper


Steroid hormones have been implicated in hepatocarcinogenesis in humans and in experimental animals. The use of oral contraceptives (OC) increases the risk of adenomas and possibly carcinomas in human liver; androgenic/anabolic steroid use has also been associated with hepatic neoplastic lesions (1–4). Furthermore, a possible role of sex steroids in hepatocarcinogenesis has been suggested by the 2.0-fold increase in male: female cancer risk ratio in areas with high exposure to aflatoxin B1, or high prevalence of hepatitis B infections (5). Induction of liver tumors has been reported in rodents after prolonged treatment with relatively high doses of several estrogens and progestins. Anabolic steroids have also been shown to induce or promote tumors in rat or mouse livers (1,4, 6, 7). As to the possible mechanisms underlying these hepatocarcinogenic effects, two major hypotheses have been considered. One hypothesis presumes that sex steroids have tumor-initiating or complete carcinogenic activity. However, when sex steroids have been tested in assays for genotoxic or mutational effects, the results have been generally negative. Recently, two synthetic compounds, tamoxifen and cyproterone acetate (CPA), have been shown to have genotoxic effects, as well as initiating and complete carcinogenic activity in rat liver (8–13). Using sensitive techniques that detect DNA adducts, weak genotoxic effects have been reported for other steroids (14); however, the relevance of these weak effects is unknown. Indeed, for most steroidal hormones the “complete carcinogen” mechanism appears unlikely. The alternative hypothesis assumes a nongenotoxic mechanism for steroid carcinogenicity. In initiation/promotion studies, several steroids were found to be liver tumor promoters (7, 13, 15). Therefore, hepatocarcinogenesis may result from promotion of initiated cells formed spontaneously in the liver (16, 17).


Ethinyl Estradiol Cyproterone Acetate Preneoplastic Cell Liver Cell Proliferation Liver Tumor Promoter 
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Copyright information

© Springer-Verlag New York, Inc. 1996

Authors and Affiliations

  • Rolf Schulte-Hermann
  • W. Bursch
  • B. Grasl-Kraupp
  • L. Müllauer
  • H. Ochs
  • W. Parzefall
  • B. Ruttkay-Nedecky

There are no affiliations available

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