Rapid activation of endothelial nitric oxide synthase by estrogen

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Estrogen is an important atheroprotective molecule that causes the rapid dilation of blood vessels by stimulating endothelial nitric oxide synthase (eNOS). There is also evidence that estrogen modulates airway epithelial NO production, thereby potentially affecting bronchial hyperresponsiveness. Studies in cultured endothelial and airway epithelial cells indicate that physiologic concentrations of estrogen cause rapid direct activation of eNOS that is unaffected by actinomycin D, but fully inhibited by estrogen receptor (ER) antagonism. Overexpression of ERα leads to marked enhancement of the acute response to estrogen, and this process is blocked by ER antagonism, it is specific to estrogen, and it requires the ERα hormone binding domain. In addition, the acute response of eNOS to estrogen can be reconstituted in COS- 7 cells cotransfected with wild-type ERα and eNOS, but not by transfection with eNOS alone. Furthermore, the inhibition of calcium influx, or tyrosine kinases or MAP kinase prevents the stimulation of eNOS by estrogen, and estrogen causes rapid ER-dependent activation of MAP kinase. These findings indicate that the acute effects of estrogen on both endothelial and airway epithelial eNOS are mediated by ERα functioning in a novel, nongenomic manner to activate the enzyme via calcium-dependent, MAP kinase-dependent mechanisms.

Original languageEnglish (US)
Pages (from-to)28-34
Number of pages7
JournalSteroids
Volume64
Issue number1-2
DOIs
StatePublished - Jan 1999

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Nitric Oxide Synthase Type III
Estrogens
Chemical activation
Estrogen Receptors
Phosphotransferases
Protein-Tyrosine Kinases
Calcium
COS Cells
Mitogen-Activated Protein Kinase Kinases
Blood vessels
Dactinomycin
Transfection
Blood Vessels
Dilatation
Epithelial Cells
Hormones
Molecules
Enzymes

Keywords

  • Estrogen
  • Estrogen receptor
  • Nitric oxide synthase
  • Steroid

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Molecular Biology

Cite this

Rapid activation of endothelial nitric oxide synthase by estrogen. / Shaul, Philip W.

In: Steroids, Vol. 64, No. 1-2, 01.1999, p. 28-34.

Research output: Contribution to journalArticle

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