Progestin regulation of plasminogen activator inhibitor type 1 in primary cultures of endometrial stromal and decidual cells.
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.
Schatz
F
F
Department of Obstetrics, Gynecology, and Reproductive Sciences, Mount Sinai School of Medicine, New York, New York 10029.
Lockwood
C J
CJ
D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen; D003656:Decidua / Q000187:drug effects / Q000378:metabolism*; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D004958:Estradiol; D003094:Collagen; D017258:Medroxyprogesterone Acetate