Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland
Cadmium mimics the in vivo effects of estrogen in the uterus and mammary gland
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DOI：
10.1038/nm902
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发表时间：
2003-08-01
期刊：
影响因子：
82.9
通讯作者：
Martin, MB
中科院分区：
文献类型：
--
作者：
Johnson, MD;Kenney, N;Martin, MB
有人认为，环境污染物模拟雌激素的作用，导致野生动物生殖系统的破坏，并导致西方人群中与雌激素有关的癌症和疾病的高发病率。先前的研究表明，在功能上，镉在乳腺癌细胞中的作用类似于甾体雌激素，因为它能够与雌激素受体的激素结合结构域形成高亲和力复合物（1，2）。本研究的结果表明，镉在体内也具有有效的雌激素样活性。暴露于镉增加子宫湿重，促进乳腺的生长和发育，并诱导卵巢切除动物的子宫调节基因。在子宫中，湿重的增加伴随着子宫内膜的增殖和孕酮受体（PgR）和补体成分C3的诱导。在乳腺中，镉促进侧枝和肺泡芽的形成和酪蛋白，乳清酸性蛋白，PgR和C3的诱导增加。在子宫内暴露于金属也模仿雌激素的影响。雌性后代经历了更早的青春期和增加上皮面积和终端芽在乳腺中的数量。
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 receptor(1,2). 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.