Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery endothelium

Todd S. Sherman, Ken L. Chambliss, Linda L. Gibson, Margaret C. Pace, Michael E. Mendelsohn, Sandra L. Pfister, Philip W. Shaul

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)610-616
Number of pages7
JournalAmerican journal of respiratory cell and molecular biology
Volume26
Issue number5
DOIs
StatePublished - Jan 1 2002

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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