Estrogen receptors α and β in the rodent mammary gland

TLDR

Estrogen is essential for mammary gland growth and function, yet the distinct roles of its two receptors, ERα and ERβ, remain unclear. Western blot analysis and sucrose gradient centrifugation were used to confirm the distinct expression patterns of ERα and ERβ in the rat mammary gland. ERα is expressed in 40 % of epithelial nuclei prepubertally, decreases to 5 % during pregnancy, and rises to 70 % during lactation, while ERβ is consistently expressed in 60–70 % of epithelial cells at all stages; co‑expression is rare during pregnancy but reaches up to 60 % during lactation, and most ERβ‑positive cells do not proliferate, indicating that these receptors are not required for estrogen‑mediated proliferation.

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, ERα and ERβ, are expressed in the rat mammary gland but the presence and cellular distribution of the two receptors are distinct. In prepubertal rats, ERα 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 ERα with up to 70% of the nuclei positive at day 21. Approximately 60–70% of epithelial cells expressed ERβ at all stages of breast development. Cells coexpressing ERα and ERβ 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 ERα-positive cells but was observed in 3–7% of ERβ-containing cells. Because more than 90% of ERβ-bearing cells do not proliferate, and 55–70% of the dividing cells have neither ERα nor ERβ, it is clear that the presence of these receptors in epithelial cells is not a prerequisite for estrogen-mediated proliferation.