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ABSTRACT: Cadmium mimics the in vivo effects of estrogen in the
uterus and mammary gland
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.
[07/14/2003; Nature Medicine]
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