Estrogen receptors α and β in the rodent mammary gland

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