Estrogen dependent regulation of estrogen receptor gene expression in normal mammary gland and its relationship to estrogenic sensitivity.

In the present study, we have examined the relationship between estradiol (E2)-dependent regulation of estrogen receptor (ER) gene expression in normal mammary glands and its relationship to progesterone receptor (PgR) gene expression using tissues from E2-sensitive and -insensitive states. Estradiol caused a time-dependent decrease in ER mRNA levels in E2-sensitive mammary glands reaching a maximum at approx 6 h, at which time the levels of PgR mRNA also reached a maximum. In contrast, in E2-insensitive mammary glands, there was no E2-dependent decrease in ER mRNA at all times tested. Experiments using dissociated cells revealed that although the epithelial cells of mammary glands from both E2-sensitive and -insensitive states contained ER mRNA, in the intact E2-sensitive mammary glands, it was the nonepithelial ER that was decreasing in response to E2. Since the epithelial cells of normal mammary glands are the primary target for E2-dependent PgR synthesis, our studies suggest that a positive correlation between E2-dependent PgR gene expression and E2-dependent downregulation of ER may simply be coincidental and may not bear any true biological relationship.