Early exposure of the rat mammary gland to estrogen and progesterone blocks co-localization of estrogen receptor expression and proliferation.
An early single full-term pregnancy induces a long-lasting protective effect against mammary tumor development in humans and rodents. This protective effect can be mimicked in rats by short-term administration of estrogen and progesterone hormones prior to carcinogen administration. The hormones of pregnancy are able to induce a proliferative block upon carcinogen challenge that is not observed in the age-matched virgin. We wished to determine whether carcinogen is needed to induce a paracrine-to-autocrine shift of proliferation in steroid receptor positive cells or if such a cell population already exists in the age-matched virgin mammary gland. Here we show that estrogen receptor positive (ER+) proliferating cells are rare in the developing mammary gland of the virgin rat but represent the majority of the proliferating cells in the mature (96-day-old) mammary gland of the virgin rat. As the majority of the proliferating cells before carcinogen challenge were ER positive, the ER+ proliferating cells in the mature mammary gland may represent the target cells for carcinogen-induced transformation. Importantly, prior exposure of the mammary gland to pregnancy levels of estrogen/progesterone blocked this positive association. This ability to block the proliferation of the ER+ cells may be one factor by which pregnancy induces protection against breast cancer.
Sivaraman
L
L
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Hilsenbeck
S G
SG
Zhong
L
L
Gay
J
J
Conneely
O M
OM
Medina
D
D
O'Malley
B W
BW
D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D001973:Bromodeoxyuridine / Q000032:analysis; D002273:Carcinogens; D002455:Cell Division; D004958:Estradiol / Q000032:analysis / Q000494:pharmacology*; D005260:Female; D005455:Fluorescent Antibody Technique; D008321:Mammary Glands, Animal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008770:Methylnitrosourea; D011374:Progesterone / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D011920:Rats, Inbred WF; D011960:Receptors, Estrogen / Q000378:metabolism*
D002273:Carcinogens; D011960:Receptors, Estrogen; D011374:Progesterone; D004958:Estradiol; D008770:Methylnitrosourea; D001973:Bromodeoxyuridine