Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery endothelium.

Prostacyclin (PGI2) is a key mediator of pulmonary vasodilation during perinatal cardiopulmonary transition, at a time when fetal plasma estrogen levels are rising. We have previously shown that estradiol-17 β (E2) rapidly stimulates nitric oxide production by ovine fetal pulmonary artery endothelial cells (PAEC), and that this occurs through nongenomic mechanisms which are calcium- and tyrosine kinase-mitogen-activated protein (MAP) kinase–dependent. In the present study, we determined if E2 acutely activates PGI2 production in PAEC. E2 (10− 8 M for 15 min) caused a 52% increase in PGI2, the threshold concentration was 10− 10 M E2, the effect occurred within 5 min, and it was not related to changes in cyclooxygenase type 1 (COX-1) or COX-2 abundance. Estrogen receptor (ER) α and ER β proteins and mRNAs were found to be constitutively expressed in PAEC, and PGI2 stimulation with E2 was fully blocked by both ER antagonism with ICI 182,780, which is not selective for either ER isoform, and the ER β -specifi...