Faculty Collaboration Database

Estrogen acutely activates prostacyclin synthesis in ovine fetal pulmonary artery endothelium. Am J Respir Cell Mol Biol 2002 May;26(5):610-6

Date

04/24/2002

Pubmed ID

11970914

DOI

10.1165/ajrcmb.26.5.4528

Scopus ID

2-s2.0-0036010528 (requires institutional sign-in at Scopus site)   75 Citations

Abstract

Prostacyclin (PGI(2)) 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-17beta (E(2)) 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 E(2) acutely activates PGI(2) production in PAEC. E(2) (10(-8) M for 15 min) caused a 52% increase in PGI(2), the threshold concentration was 10(-10) M E(2), 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) alpha and ER beta proteins and mRNAs were found to be constitutively expressed in PAEC, and PGI(2) stimulation with E(2) was fully blocked by both ER antagonism with ICI 182,780, which is not selective for either ER isoform, and the ER beta-specific antagonist RR-tetrahydrochrysene. The rapid response to E(2) was also inhibited by calcium chelation, whereas genistein- or PD98059-induced inhibition of tyrosine kinase and MAP kinase kinase, respectively, had no effect. Thus, E(2) causes rapid stimulation of PGI(2) synthesis in fetal PAEC, this process is mediated by ER beta, and it is calcium-dependent and tyrosine kinase-MAP kinase-independent. These mechanisms may play a role in pulmonary vasodilation in the perinatal period.

Author List

Sherman TS, Chambliss KL, Gibson LL, Pace MC, Mendelsohn ME, Pfister SL, Shaul PW

Author

Sandra L. Pfister PhD Professor in the Pharmacology and Toxicology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cells, Cultured
Chelating Agents
Cyclooxygenase 1
Cyclooxygenase 2
Dose-Response Relationship, Drug
Endothelium, Vascular
Enzyme Inhibitors
Epoprostenol
Estradiol
Estrogen Antagonists
Estrogen Receptor alpha
Estrogen Receptor beta
Immunoblotting
Isoenzymes
Mitogen-Activated Protein Kinase Kinases
Prostaglandin-Endoperoxide Synthases
Protein-Tyrosine Kinases
Pulmonary Artery
RNA, Messenger
Receptors, Estrogen
Sheep
Signal Transduction