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Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland

Nature Medicine volume 9, pages 1081–1084 (2003)Cite this article

Abstract

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.

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Figure 1: Histological effects of cadmium in the uteri of ovariectomized rats treated with cadmium, estradiol or ICI-182,780 (ICI).
Figure 2: Effects of cadmium on the expression of PgR and C3 in ovariectomized animals treated with cadmium, estradiol or ICI-182,780.
Figure 3: Effect of in utero exposure to cadmium on the mammary gland in female offspring.

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Acknowledgements

We thank M.E. Lippman for helpful discussions, R. Newbold for helpful discussions and critical reading of the manuscript, and A. Murray, I. Onojafe, G. Montenegro, A. Foxworth, D. Raval and W. Jefferson for technical assistance. This work was supported by National Institutes of Health grant CA70708, Cancer Research Foundation of America, The Susan G. Komen Foundation and an anonymous donation. Support for tissue culture, animal care and histopathology core facilities was provided by P50-CA58185 and P30-CA51008.

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Author notes

  1. Michael D Johnson, Nicholas Kenney and Adriana Stoica: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, 20007, DC, USA

    Michael D Johnson, Adriana Stoica, Leena Hilakivi-Clarke, Baljit Singh, Gloria Chepko, Robert Clarke, Peter F Sholler, Apolonio A Lirio, Ronald Reiter, Bruce Trock & Mary Beth Martin

  2. Department of Biology, Hampton University, Hampton, 23668, Virginia, USA

    Nicholas Kenney

  3. Department of Chemistry, Georgetown University, Washington, 20007, DC, USA

    Colby Foss

  4. University of Pittsburgh, Pittsburgh, 15238, Pennsylvania, USA

    Soonmyoung Paik

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Correspondence to Mary Beth Martin.

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Johnson, M., Kenney, N., Stoica, A. et al. Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland. Nat Med 9, 1081–1084 (2003). https://doi.org/10.1038/nm902

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