Inhibition of progesterone receptor function results in loss of basic fibroblast growth factor expression and stromal cell proliferation during uterine remodelling in the pregnant rat

Abstract

Recent studies suggest that hormonal control of uterine cell proliferation may be moderated by polypeptide growth factors. It remains to be determined, however, whether growth factors cause or are the consequence of hormone action. Basic fibroblast growth factor (bFGF) has been shown to influence cell proliferation and differentiation of a variety of mesoderm-derived cells. To elucidate the regulatory mechanisms controlling stromal cell proliferation and differentiation required for embryo implantation further, immunohistochemical localization of the progesterone receptor and bFGF have been studied. The cell-specific distribution of these proteins was determined in the rat uterus during early pregnancy and after injection of the progesterone receptor antagonist mifepristone (RU 486) at days 1 and 2 post coitum (p.c.) to block implantation. Cell division was restricted to luminal and glandular epithelial cells in pregnant and RU 486-treated rats at day 3 p.c. At day 4 of pregnancy, cell proliferation switched from the epithelia to the stroma in pregnant rats, but after RU 486 treatment division of stromal cells was inhibited significantly (P < 0.05). Progesterone receptor distribution was altered and bFGF was absent in RU 486-blocked stromal cells. Expression of bFGF in luminal and glandular epithelial cells, however, was insensitive to the effects of progesterone receptor antagonism. bFGF content was stimulated in the luminal epithelium and in decidual cells by the implanting embryo. These results indicate that repression of progesterone receptor function in early pregnancy results in a cell-specific loss of bFGF from stromal cells and inhibition of their proliferation. The results further suggest that the regulation of endometrial cell bFGF content is modulated at the site of implantation by the embryo.