| First Author | Winuthayanon W | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 45 | Pages | 19272-7 |
| PubMed ID | 20974921 | Mgi Jnum | J:167551 |
| Mgi Id | MGI:4868534 | Doi | 10.1073/pnas.1013226107 |
| Citation | Winuthayanon W, et al. (2010) Uterine epithelial estrogen receptor alpha is dispensable for proliferation but essential for complete biological and biochemical responses. Proc Natl Acad Sci U S A 107(45):19272-7 |
| abstractText | Female fertility requires estrogen to specifically stimulate estrogen receptor alpha (ERalpha)-dependent growth of the uterine epithelium in adult mice, while immature females show proliferation in both stroma and epithelium. To address the relative roles of ERalpha in mediating estrogen action in uterine epithelium versus stroma, a uterine epithelial-specific ERalpha knockout (UtEpialphaERKO) mouse line was generated by crossing Esr mice with Wnt7a-Cre mice. Expression of Wnt7a directed Cre activity generated selective deletion of ERalpha in uterine epithelium, and female UtEpialphaERKO are infertile. Herein, we demonstrate that 17beta-estradiol (E(2))-induced uterine epithelial proliferation was independent of uterine epithelial ERalpha because DNA synthesis and up-regulation of mitogenic mediators were sustained in UtEpialphaERKO uteri after E(2) treatment. IGF-1 treatment resulted in ligand-independent ER activation in both wild-type (WT) and UtEpialphaERKO and mimicked the E(2) stimulatory effect on DNA synthesis in uterine epithelium. Uterine epithelial ERalpha was necessary to induce lactoferrin, an E(2)-regulated secretory protein selectively synthesized in the uterine epithelium. However, loss of uterine epithelial ERalpha did not alter the E(2)-dependent progesterone receptor (PR) down-regulation in epithelium. Strikingly, the uterine epithelium of UtEpialphaERKO had robust evidence of apoptosis after 3 d of E(2) treatment. Therefore, we surmise that estrogen induced uterine hyperplasia involves a dispensable role for uterine epithelial ERalpha in the proliferative response, but ERalpha is required subsequent to proliferation to prevent uterine epithelial apoptosis assuring the full uterine epithelial response, illustrating the differential cellular roles for ERalpha in uterine tissue and its contribution during pregnancy. |
