ABSTRACT 1887 _Pulmonary Vascular Biology Platform, Monday, 5/3_ Prostacyclin is a critical mediator of vascular function and growth in the developing lung, where it is produced primarily by

the vascular endothelium. A variety of studies in intact animal models indicate that prostacyclin plays a key role in the acute vasodilation of the pulmonary circulation at the time of

birth. This is occurring at a time when fetal plasma estrogen levels are rapidly rising due to marked enhancement in placental estrogen synthesis following the onset of parturition. We have

previously demonstrated that physiologic levels of estradiol (10-10 to 10-8M) stimulate the production of the vasodilator nitric oxide by ovine fetal pulmonary artery endothelial cells

caused a 52% increase in prostacyclin synthesis compared to basal levels (256±30 vs 167±16 pg/well, respectively). The response was evident at 10-10M 17β-estradiol, and it occurred within 5

min of exposure to the hormone. There was no change in prostacylin production in response to 17α-estradiol (10-8 to 10-6M), indicating that the effect is unique to 17β-estradiol. Immunoblot

analysis revealed comparable cyclooxygenase type 1 expression and a lack of cyclooxygenase type 2 in control and stimulated cells, signifying that the rapid response is not due to changes in

the abundance of the rate-limiting enzyme in prostacyclin synthesis. Thus, the acute mechanism differs significantly from the effects of prolonged 17β-estradiol exposure, which we have

previously shown upregulates cyclooxygenase type 1 mRNA and protein expression after 48 h. To determine the potential role of estrogen receptors (ER) in the rapid activation of prostacyclin

production, studies were performed in the absence or presence of the ER antagonist ICI 182,780 (10-5M). Concomitant acute treatment with the ICI compound completely prevented

17β-estradiol-induced increases in prostacyclin production. RT-PCR assays and immunoblot analysis revealed expression of the alpha isoform of ER in the PAEC, whereas expression of the beta

isoform was not detected. These findings indicate that physiologic concentrations of estradiol cause rapid stimulation of prostacyclin synthesis in fetal PAEC, and that this process is

mediated by ER activation. The response most likely involves ERα, but further experiments will be required to exclude the potential role of a previously unknown ER subtype. These mechanisms

may underly estrogen-induced vasodilation in both pulmonary and nonpulmonary vascular beds. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Dept. of Pediatrics, University of Texas

Southwestern Medical Center, Dallas, TX Todd S Sherman, Ken L Chambliss, Margaret C Pace & Philip W Shaul Authors * Todd S Sherman View author publications You can also search for this

author inPubMed Google Scholar * Ken L Chambliss View author publications You can also search for this author inPubMed Google Scholar * Margaret C Pace View author publications You can also

search for this author inPubMed Google Scholar * Philip W Shaul View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and

permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Sherman, T., Chambliss, K., Pace, M. _et al._ Estrogen Acutely Activates Prostacyclin Synthesis in Ovine Fetal Pulmonary Artery Endothelial

Cells. _Pediatr Res_ 45, 320 (1999). https://doi.org/10.1203/00006450-199904020-01903 Download citation * Issue Date: 01 April 1999 * DOI: https://doi.org/10.1203/00006450-199904020-01903

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