Progesterone regulation of epidermal growth factor receptor in rat decidua basalis during pregnancy

Ovarian steroid hormones and epidermal growth factor (EGF) play important interactive roles in proliferation and decidualization of mesometrial stromal cells during pregnancy. This study determined the ontogeny of EGF receptor (EGF-R) expression in the decidua basalis (DB) throughout pregnancy and its regulation by estrogen and progesterone (P4). DB were isolated from rats between Days 8-21 of pregnancy and prepared for immunohistochemistry or Western analysis. In one study, rats were ovariectomized (Ovx) on Day 8 or 9 and given estradiol-17beta, P4, or both. In another study, the antiprogestin, mifepristone (RU-486), was administered on Day 9. During normal pregnancy, total EGF-R (phosphorylated and unphosphorylated forms) increased from Day 8 to a maximum level on Days 10 and 12. Tyrosine-phosphorylated EGF-R (pEGF-R), the bioactive form, was also highest on Days 10 and 12. Both forms of receptor decreased to almost undetectable levels during DB regression on Days 17-21. Immunohistochemistry of DB from Ovx rats revealed that only P4 was able to maintain normal expression of EGF-R; RU-486 decreased EGF-R expression within 6 h, and by 24 h EGF-R and pEGF-R were 15% of the Day 10 control group levels. These findings show that EGF-R is a P4-dependent protein associated with stromal cell proliferation and decidualization.