Michael D Johnson1, 5, Nicholas Kenney2, 5, Adriana Stoica1, 5, Leena Hilakivi-Clarke1, Baljit Singh1, Gloria Chepko1, Robert Clarke1, Peter F Sholler1, Apolonio A Lirio1, Colby Foss3, Ronald Reiter1, Bruce Trock1, Soonmyoung Paik4 & Mary Beth Martin1
It has been suggested that environmental contaminants that mimic the effects of estrogen contribute to disruption of the reproductive systems of animals in the wild, and to the high incidence of hormone-related cancers and diseases in Western populations. Previous studies have shown that functionally, cadmium acts like steroidal estrogens in breast cancer cells as a result of its ability to form a high-affinity complex with the hormone binding domain of the estrogen receptor1, 2. The results of the present study show that cadmium also has potent estrogen-like activity in vivo. Exposure to cadmium increased uterine wet weight, promoted growth and development of the mammary glands and induced hormone-regulated genes in ovariectomized animals. In the uterus, the increase in wet weight was accompanied by proliferation of the endometrium and induction of progesterone receptor (PgR) and complement component C3. In the mammary gland, cadmium promoted an increase in the formation of side branches and alveolar buds and the induction of casein, whey acidic protein, PgR and C3. In utero exposure to the metal also mimicked the effects of estrogens. Female offspring experienced an earlier onset of puberty and an increase in the epithelial area and the number of terminal end buds in the mammary gland.
1. Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
2. Department of Biology, Hampton University, Hampton, Virginia 23668, USA.
3. Department of Chemistry, Georgetown University, Washington, DC 20007, USA.
4. University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA.
5. These authors contributed equally to this work.
Correspondence should be addressed to M B Martin. e-mail: martinmb@georgetown.edu
source: http://www.nature.com/cgi-taf/DynaPage.taf?file=/nm/journal/v9/n8/abs/nm902.html 6oct03
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