Estrogen receptors alpha and beta in the rodent mammary gland

An obligatory role for estrogen in growth, development, and functions of th e mammary gland is well established, but the roles of the two estrogen rece ptors remain unclear. With the use of specific antibodies, it was found tha t both estrogen receptors, ER alpha and ER beta, are expressed in the rat m ammary gland but the presence and cellular distribution of the two receptor s are distinct. In prepubertal rats, ER alpha was detected in 40% of the ep ithelial cell nuclei. This decreased to 30% at puberty and continued to dec rease 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. West ern blot analysis and sucrose gradient centrifugation confirmed this patter n of expression. During pregnancy, the proliferating cell nuclear antigen w as 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 no t proliferate, and 55-70% of the dividing cells have neither ER alpha nor E R beta, it is clear that the presence of these receptors in epithelial cell s is not a prerequisite for estrogen-mediated proliferation.