Estrogen receptors alpha and beta in rat decidua cells: Cell-specific expression and differential regulation by steroid hormones and prolactin

Estradiol is known to play an important role in the growth and differentiat ion of rat uterine stromal cells into decidual cells. In particular, this h ormone with progesterone is necessary for blastocyst implantation and subse quent decidualization in the rat. Although binding experiments have demonst rated the presence of estrogen-binding sites, no evidence exists as to whet her the rat decidua expresses both isoforms of the estrogen receptor (ER), alpha and beta. In this investigation, we analyzed the expression of decidu al ER alpha and ER beta, studied their regulation by PRL and steroid hormon es and examined the ability of decidual ERP to transduce the estradiol sign al to the progesterone receptor. Immunocytochemistry, RT-PCR, and Northern blot analysis showed that both ER species are coexpressed in the decidua du ring pseudopregnancy. Interestingly, these genes were preferentially found in a cell population localized in the antimesometrial site of the uterus wh ere blastocyst implantation takes place. Using decidual cells in primary cu lture obtained from pseudopregnant rats and a decidua-derived cell line (GG -AD), we show a differential regulation of ER alpha and ER beta by PRL and ovarian steroid hormones. Whereas PRL, estradiol, and progesterone all incr eased ER beta messenger RNA (mRNA) expression in a dose-dependent manner, o nly PRL up-regulated the mRNA levels of ER alpha. Estradiol had no effect o n ER alpha expression, whereas progesterone markedly decreased its mRNA lev els. Interestingly, progesterone, which up-regulates the ability of PRL to signal to a PRL-regulated gene in mammary-gland derived cells, prevented PR L stimulation of decidual ER alpha and had no synergistic effect on ER beta expression. The use of GG-AD cells, which express only ER beta, allowed us to demonstrate that this receptor subtype is functional and transduces est radiol signal to the progesterone receptor. In summary, the results of this investigation have revealed that ER beta is expressed in addition to ER al pha in the rat decidua, and that the expression of both ERs are cell specif ic and differentially regulated by PRL and steroids. One salient finding of this investigation is that progesterone down-regulates ER alpha, but conco mitantly increases the expression of a functional ER beta that mediates est radiol up-regulation of the decidual progesterone receptor.