Journal of Clinical Endocrinology & Metabolism, Vol 77, 621-625, Copyright © 1993 by Endocrine Society

ARTICLES

Progestin regulation of plasminogen activator inhibitor type 1 in primary cultures of endometrial stromal and decidual cells

F Schatz and CJ Lockwood
Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, New York, New York 10029.

The progestin medroxyprogesterone acetate (MPA) enhanced expression of the endothelial-type plasminogen activator inhibitor PAI-1 by stromal cells from cycling endometrium and by decidual cells from first trimester endometrium. In the cultured stromal cells, Northern analysis revealed a 4-fold increase in steady state levels of PAI-1 mRNA in response to 10(-6)-10(-8) mol/L MPA. Although the cells were refractory to 10(-8) mol/L estradiol (E2) alone, E2 plus MPA produced a further doubling of PAI-1 mRNA levels. Parallel effects on PAI-1 protein levels in the stromal cell-conditioned medium were measured by immunoassay and confirmed by immunoblot analysis. During an initial 3-day exposure, PAI- 1 levels were elevated 6- and 12-fold by MPA and E2 plus MPA, respectively, compared with those in either control or E2-treated cells. In the subsequent 3 days of culture, PAI-1 levels were increased 30-fold by MPA and 70-fold by E2 plus MPA. Cultured decidual cells released significant quantities of PAI-1 under basal conditions; these levels were also elevated by MPA and increased markedly by E2 plus MPA. While PAI-2 was also detected in both stromal and decidual cell cultures, its levels were far lower than those of PAI-1 and were unaffected by exogenous steroids. Extrapolation of these in vitro results to periimplantational events in humans suggests that under progesterone regulation, decidual cell-derived PAI-1 could 1) restrain blastocyst invasion of the stroma by inhibiting trophoblast-associated urokinase-type plasminogen activator, and 2) prevent hemorrhage during trophoblast invasion of the endometrial vasculature by inhibiting fibrinolysis mediated by tissue-type plasminogen activator.

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