Estrogen receptors α and β in the rodent mammary gland

Abstract

An obligatory role for estrogen in growth, development, and functions of the mammary gland is well established, but the roles of the two estrogen receptors remain unclear. With the use of specific antibodies, it was found that both estrogen receptors, ER␣ and ER␤, are expressed in the rat mammary gland but the presence and cellular distribution of the two receptors are distinct. In prepubertal rats, ER␣ was detected in 40% of the epithelial cell nuclei. This decreased to 30% at puberty and continued to decrease throughout pregnancy to a low of 5% at day 14. During lactation there was a large induction of ER␣ with up to 70% of the nuclei positive at day 21. Approximately 60 -70% of epithelial cells expressed ER␤ at all stages of breast development. Cells coexpressing ER␣ and ER␤ were rare during pregnancy, a proliferative phase, but they represented up to 60% of the epithelial cells during lactation, a postproliferative phase. Western blot analysis and sucrose gradient centrifugation confirmed this pattern of expression. During pregnancy, the proliferating cell nuclear antigen was not expressed in ER␣-positive cells but was observed in 3-7% of ER␤-containing cells. Because more than 90% of ER␤-bearing cells do not proliferate, and 55-70% of the dividing cells have neither ER␣ nor ER␤, it is clear that the presence of these receptors in epithelial cells is not a prerequisite for estrogen-mediated proliferation. E strogens are potent mitogens in the mammary gland, where they are obligatory for normal development as well as for induction and progression of mammary carcinoma (1). The female mammary gland undergoes a surge of cell division during puberty, and throughout adult life there is cyclical proliferation and involution during estrous cycles (2). Despite the clear role for estrogen in proliferation of the mammary epithelium, the role of estrogen receptors in this process remains unclear. During pubertal growth and during the estrous cycle, the majority of proliferating cells, both in terminal end buds and in ducts, do not contain estrogen receptor ␣ (ER␣). This has been observed in both rodent (3) and human (4, 5) mammary glands. Progesterone receptor (PR) is localized in those cells that contain ER␣, and induction of PR by estrogen occurs at much lower plasma levels of estrogen than are required for cell proliferation (5). These observations have led to the concept (6) of two distinct types of responses to estrogen in the breast: (i) an indirect action of estradiol in the mammary epithelium by inducing estrogen receptor-containing stromal cells to produce growth factors that stimulate epithelial cells to divide and (ii) a direct effect on ER␣-containing cells that occurs at low estrogen concentrations and results in induction of PR.Dependence of epithelium on stroma for estrogen-mediated induction of PR has been demonstrated in experiments in which epithelial and stromal components were cultured together (7-9). Stroma from responsive (mature) glands can confer estrogen sensitivity on epithelium from insensitiv...

Estrogen receptor β acts as a dominant regulator of estrogen signaling

“…A recent study describes coexpression of ERa and ERb protein in mouse mammary gland at di erent developmental stages (Saji et al, 2000). ERb protein has also been demonstrated to be expressed in rat cardiac myocytes and ®broblasts where ERa is also present (Grohe et al, 1997(Grohe et al, , 1998.…”

RETRACTED ARTICLE: Regulation of estrogen receptor signaling in breast carcinogenesis and breast cancer therapy

“…Analysis of estrogen receptor proteins in rat mammary gland has shown that both types of ERs are expressed and the results from ERα-KO and ERβ-KO mice reveal that ERα is necessary for mammary gland development. ERβ co-expression with ERα has been suggested to repress ERα's function and may contribute to the insensitivity of the mammary gland to estrogen during lactation [31,32]. Deletion of ERα, which mediates the E2 action in mice, results in a rudimentary ductal system that fails to branch out [33].…”

Spatiotemporal dynamics of the expression of estrogen receptors in the postnatal mouse brain

“…Chicken polyclonal anti-ERb1 antibody, chicken polyclonal anti-ERb ins antibody, and rabbit polyclonal anti-ERbLBD antibody were produced in our laboratory. 11 Mouse monoclonal anti-NeuN antibody was from Chemicon (Temecula, CA, USA). Biotinylated anti-rabbit, anti-chicken, and anti-mouse antibodies raised in goats were from Zymed (South San Francisco, CA, USA).…”

“…After the discovery of ERb, 10 it became essential to reexamine the protein map of ERs in the CNS using antibodies that can selectively recognize ERa or ERb. 11 There have been several reports of ERa and ERb1 localization in the brain, 12,13 but a profile of receptor expression with age is lacking. In the previous IHC study from our group, using a highly specific antibody against ERb1 (ERb 503 IgY), we showed a highlevel expression of ERb1 14 and its importance during embryogenesis.…”