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 receptor. 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.
Johnson
Michael D
MD
Department of Oncology, Lombardi Cancer Center, Georgetown University, Washington, DC 20007, USA.
Kenney
Nicholas
N
Stoica
Adriana
A
Hilakivi-Clarke
Leena
L
Singh
Baljit
B
Chepko
Gloria
G
Clarke
Robert
R
Sholler
Peter F
PF
Lirio
Apolonio A
AA
Foss
Colby
C
Reiter
Ronald
R
Trock
Bruce
B
Paik
Soonmyoung
S
Martin
Mary Beth
MB
D000818:Animals; D002104:Cadmium / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002364:Caseins / Q000235:genetics / Q000378:metabolism; D003176:Complement C3 / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology*; D045166:Estradiol Congeners / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism; D018716:Molecular Mimicry; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D012741:Sexual Maturation / Q000187:drug effects; D014599:Uterus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D002364:Caseins; D003176:Complement C3; D045166:Estradiol Congeners; D004965:Estrogen Antagonists; D008894:Milk Proteins; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C024471:whey acidic proteins; D002104:Cadmium; D000077267:Fulvestrant; D004958:Estradiol