Molecular Mechanisms of Estrogen Carcinogenesis

In western society, the causes of several cancers--including breast, endometrium, ovary, liver, and prostate--have been linked to inappropriate and/or prolonged exposure to synthetic or endogenous steroidal hormones. In this review, we discuss the mechanisms of estrogen carcinogenesis with a focus on estrogen metabolism to 16 alpha-hydroxy estrone and 2- and 4-hydroxy catechol estrogens and the potential effects of these metabolites in vitro and in vivo on hamster liver and kidney and rat liver carcinogenesis models. The examples demonstrate that the parent compounds and their metabolites cause both nongenotoxic cell proliferative effects as well as direct and indirect genotoxic effects, which illustrates the complex nature of estrogen carcinogenesis. These effects, in combination with the metabolic state of the tissue and the timing of its exposure, may determine the cell type (organ) of tumor development and the severity of disease.