3 Prostaglandins and growth factors in the endometrium

Abstract

Prostaglandins are the products of cyclo-oxygenase and endoperoxide breakdown of free intracellular arachidonic acid (AA). Arachidonic acid is cleaved from membrane phospholipids by phospholipase A2 (PLA2) and phospholipase C (PLC). The human placenta is a rich source of lipocortin like PLA2 inhibitors. Human endometrium contains both PLA2 and PLC activity, and it is under research which pathway is predominant. Prostaglandin F2-alpha is derived from PLC endoperoxide, while prostaglandin E2 is formed by degradation of PG endoperoxide. Dated studies have found that prostaglandin F2-alpha was the predominant PG in the endometrium, whereas concentrations of PGE2 did not change during the cycle. In women estradiol stimulates PG synthesis from glands, and it has a role in mediating intracellular calcium in the human. Progesterone reduces the release of PGs from endometrial explants maintained in culture, while anti-progestins RU486 and ZK98734 stimulate the release of PGs from glandular cells of decidua. There seems to be a direct effect of progesterone on expression of PG synthetase, on the expression of a PG synthesis inhibitory protein, or an effect on a PLA2 activating protein. ZK98734 does not alter the metabolism of PGF2-alpha in the absence of added AA. Calmodulin also plays a role in regulating PG synthesis. Verapamil suppresses basal release of PGF2-alpha and prevents the rise in PG release caused by ZK98734. Progesterone suppresses PG synthesis in human endometrium. Colony stimulating factor- 1 (CSF-1) stimulates Ishikawa cell proliferation, acts on the hemopoietic system, and promotes the release of cytokines like interleukin-2, tumor necrosis factor (TNF), and interferons. Transforming growth factor alpha (TGF-alpha) mediates wound healing by promoting epithelial proliferation and angiogenesis and repairs desquamated endometrium. Epidermal growth factor (EGF) is present in the luminal surface of epithelial cells and myometrium but not in stromal cells. EGF p[lays a role in the proliferation of human endometrium and steroids modify this effect. INsulin-like growth factor (IGF-1) potentiates the activities of other mitogens like EGF. Basic fibroblast growth factor (bFGF) and acidic FGF (aFGF) have been detected in the uterine flushings and tissue of the guinea pig. FGF is a mediator of angiogenesis. different PGs affect vascular contractility, hemostasis, and myometrial contractility. PG synthesis is linked to menstrual dysfunction. The functions of growth factors and PGs may be related reflecting the autocrine and paracrine regulation of endometrial cell proliferation, a topic still under study.