ENDOTHELIN-1 STIMULATES PROSTAGLANDIN-F2-ALPHA RELEASE FROM HUMAN ENDOMETRIUM

Despite a key role in the pathogenesis of menorrhagia, the factors controlling the uterine vascular bed are poorly understood. This study has assessed the effects of the potent vasoconstrictor endothelin (ET)-1 on prostaglandin (PG) release from human endometrial explants in short-term culture. There was no significant difference between the production of PGF2-alpha in proliferative and secretory tissue (1709 and 2434 pg/mg/h - median values, range 70 3745 and 219 6700 pg/mg/h). Less PGE was released than PGF2-alpha, and the amount did not vary with the phase of the menstrual cycle (308 and 296 pg/mg/h (range 65 387 and 105 429) for proliferative and secretory tissue). ET-1 (10 and 100 nM) and arachidonic acid (AA, 30-mu-M), stimulated PGF2-alpha release from proliferative, but not secretory endometrium, by 78%, 86% (P < 0.01) and 80% respectively, compared with control tissue. No effect was seen on PGE release. ET-1 may play a role in the local control of the endometrial vascular bed either directly, or via the release of PGF2-alpha.