SECRETION OF PLASMINOGEN-ACTIVATOR BY CULTURED RAT ENDOMETRIAL STROMAL CELLS FROM UTERI DIFFERENTIALLY SENSITIZED FOR THE DECIDUAL CELL REACTION

Endometrial stromal cells from rat uteri differentially sensitized for the decidual cell reaction in vivo and which undergo differing degree s of decidualization in vitro were cultured and plasminogen activator (PA) in the medium determined. The cells were obtained by enzymatic di spersion from the uteri of ovariectomized, steroid-treated rats at the equivalent of day 4, 5, or 6 of pseudopregnancy or on day 5 from rats treated on day 4 with 0, 0.3, or 1.0 mu g estradiol (low, intermediat e, or high dose of estradiol, respectively) and cultured for 24, 48, o r 72 hr. For cells from day 4, 5, and 6 uteri cultured under control c onditions, PA activity in the medium was greatest for day 5 cells, whi ch were from uteri maximally sensitized for decidualization both in vi vo and in vitro. By contrast, for cells from low-, intermediate-, and high-estradiol uteri, PA activity in the medium was greatest for the h igh-estradiol cells; these cells do not undergo decidualization in viv o or in vitro to the same extent as intermediate-estradiol cells. Indo methacin, an inhibitor of prostaglandin (PG) synthesis, reduced PGE(2) accumulation to nondetectable amounts and for most cultures decreased PA activity in the medium, suggesting that endogenous PG production r egulated in part PA secretion under control conditions. The addition o f PGE(2) with indomethacin increased PA activities above those under c ontrol conditions, but activities were still lower for day 4 and 6 cel ls compared with day 5 cells, and for low- and intermediate-estradiol cells compared with high-estradiol cells. This indicates that the diff erences in PA secretion are not explainable by differences in PGE(2) p roduction. Northern blot analysis of RNA from cells cultured for 72 hr under control conditions did not reveal significant differences in st eady-state concentrations of mRNA for urokinase-type PA or plasminogen activator inhibitor 1, but those for tissue-type PA were lower in day 6 cells compared with day 4 and 5 cells. It is concluded that PA acti vity secreted by the cultured endometrial stromal cells, although cont rolled in part by the endocrine milieu to which they were exposed prio r to culture, does not simulate decidualization in vitro and, therefor e, that PA activity is not a marker for decidualization in vitro. (C) 1998 Wiley-Liss, Inc.