TY - JOUR
T1 - Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery endothelium
AU - Sherman, Todd S.
AU - Chambliss, Ken L.
AU - Gibson, Linda L.
AU - Pace, Margaret C.
AU - Mendelsohn, Michael E.
AU - Pfister, Sandra L.
AU - Shaul, Philip W.
PY - 2002
Y1 - 2002
N2 - 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-17β (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 ERβ 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 ERβ-specific antagonist RR-tetrahydrochrysene. The rapid response to E2 was also inhibited by calcium chelation, whereas genisteinor PD98059-induced inhibition of tyrosine kinase and MAP kinase kinase, respectively, had no effect. Thus, E2 causes rapid stimulation of PGI2 synthesis in fetal PAEC, this process is mediated by ERβ, and it is calcium-dependent and tyrosine kinase-MAP kinase-independent. These mechanisms may play a role in pulmonary vasodilation in the perinatal period.
AB - 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-17β (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 ERβ 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 ERβ-specific antagonist RR-tetrahydrochrysene. The rapid response to E2 was also inhibited by calcium chelation, whereas genisteinor PD98059-induced inhibition of tyrosine kinase and MAP kinase kinase, respectively, had no effect. Thus, E2 causes rapid stimulation of PGI2 synthesis in fetal PAEC, this process is mediated by ERβ, and it is calcium-dependent and tyrosine kinase-MAP kinase-independent. These mechanisms may play a role in pulmonary vasodilation in the perinatal period.
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U2 - 10.1165/ajrcmb.26.5.4528
DO - 10.1165/ajrcmb.26.5.4528
M3 - Article
C2 - 11970914
AN - SCOPUS:0036010528
SN - 1044-1549
VL - 26
SP - 610
EP - 616
JO - American journal of respiratory cell and molecular biology
JF - American journal of respiratory cell and molecular biology
IS - 5
ER -