Progestin-regulated expression of tissue factor in decidual cells: implications in endometrial hemostasis, menstruation and angiogenesis

摘要: Expression of tissue factor (TF), the primary initiator hemostasis via thrombin formation, is induced during progesterone (P4)-stimulated decidualization human endometrial stromal cells (HESCs), and remains elevated in decidualized HESCs luteal gestational endometrium. In HESC monolayers, progestins elevate TF mRNA protein levels estradiol (E2) plus progestin further enhance for weeks despite no response to E2 alone. This vitro model mimics chronic differential ovarian steroid upregulation associated with vivo decidualization. After incubation expression, antiprogestin RU486 completely reversed this upregulation. Thus, withdrawal transformed decidualization-associated phase endometrium hemorrhagic milieu menstruation. Transient transfections promoter constructs containing SP EGR-1 binding sites before after inactivation by site-directed mutagenesis revealed that Sp1 mediates basal progestin-enhanced transcriptional activity. Progesterone receptor involvement expression was confirmed since a pure antagonist progestin-enhanced, but not basal, Sp1-mediated Enhanced require co-incubation epidermal growth (EGFR) agonist indicating EGFR expression. A peak angiogenic agent, vascular endothelial (VEGF) may be indirectly regulated P4. Neither E2, nor progestin, affected VEGF glandular epithelial cells, whereas enhanced HESCs, cells. Transudation clotting factors perivascular decidual cell would generate thrombin, enabling it act as an autocrine enhancer HESCs. Abnormal uterine bleeding complicates long-term only contraceptive use. Norplant administration, are selectively at sites. Over-expressed causes blood vessels become leaky, increasing access HESC-expressed promote feed-forward formation. Since induce angiogenesis separate receptors, they synergize elicit aberrant angiogenesis, ultimately lead focal bleeding.