Plasminogen activator inhibitor 2 in menstrual endometrium and in primary cultures of endometrial cells

Summary The objective was to study content, distribution, and cyclic variation of plasminogen activator inhibitor 2 (PAI-2) in human endometrial tissue and secretion. Regulation of PAI-2 by steroid hormones and growth factor was further studied in primary cultures of endometrial cells. Endometrial secretion and menstrual discharge was obtained from healthy volunteers, and endometrial tissue from patients at operation. PAI-2 was assayed with an ELISA in endometrial section, menstrual discharge, tissue homogenates, and conditioned media. Furthermore, endometrial tissue was analyzed with immuno-histochemistry. PAI-2 was found in very low concentrations in extracts of normal non-pregnant human endometrium, and was released to the uterine cavity in small quantities without any difference between the proliferative and secretory phases. Also, no specific immuno-staining for PAI-2 was seen in the proliferative and secretory phases. However, in menstrual endometrium certain cells in the stroma stained positive for PAI-2, and the concentration of PAI-2 was high in menstrual blood. Endometrial cells obtained in the proliferative, as well as in the secretory phases, contained significant amounts of PAI-2 after three days culture. A minor fraction was released from the stromal cells, but not from the epithelial cells. Intracellular PAI-2 was in its low molecular weight form, while both the low and high molecular weight forms were secreted in stromal cell cultures. Treatment of the cell cultures with estradiol, progesterone, DH-testosterone, epidermal growth factor, transforming growth factor α, and basic fibroblast growth factor affected neither the content nor the release of PAI-2. Significant levels of PAI-2 were associated only with the menstrual phase in vivo, whereas cultured endometrial cells, obtained in the proliferative and secretory phases, expressed PAI-2. Thus, PAI-2 production in primary cultures of endometrial cells seems to be an in vitro phenomenon.