Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells

Mitsutoshi Tamura, Santanu Deb, Siby Sebastian, Kunihiro Okamura, Serdar E. Bulun*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Objective To investigate the effects of 17β-estradiol (E2) on cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE 2) synthesis in primary human uterine microvascular endothelial cells (HUMEC). Design Prospective study. Setting Basic research laboratory at an academic medical center. Patient(s) Primary HUMEC of three women donors and primary human dermal microvascular endothelial cells of three women donors (as control), purchased from a third-party source. Intervention(s) The HUMEC were cultured in specific media in a humidified atmosphere with 5% CO2 at 37°C. Main outcome measure(s) Measures of COX-2 mRNA and protein, PGE 2 production, and estrogen receptor α and β mRNA and protein. Result(s) Treatment with E2 (10-10 to 10 -6 M) increased COX-2 mRNA levels by 2.3-fold to 2.4-fold in HUMEC. Treatment of HUMEC with E2 (10-8 M) resulted in a time-dependent increase of COX-2 mRNA levels. This was accompanied by a 2.8-fold increase in COX-2 protein level and a 1.5-fold increase in PGE2 synthesis. Pretreatment of HUMEC with a selective COX-2 inhibitor, NS-398, abolished E2-induced PGE2 synthesis, suggesting that E2 specifically up-regulates COX-2 activity. The estrogen receptor antagonist ICI 182,780 fully reversed the stimulation of COX-2 mRNA and protein levels and PGE2 synthesis by E2. Interestingly, estrogen receptor β mRNA and protein were abundant in HUMEC, whereas estrogen receptor α mRNA or protein was barely detectable. Conclusion(s) We conclude that various levels of E2 can significantly increase COX-2 expression and PGE2 synthesis in HUMEC via the estrogen receptor.

Original languageEnglish (US)
Pages (from-to)1351-1356
Number of pages6
JournalFertility and Sterility
Volume81
Issue number5
DOIs
StatePublished - May 2004

Keywords

  • Cyclooxygenase-2
  • endometriosis
  • endometrium
  • endothelial cell
  • estrogen receptor
  • prostaglandin E, estrogen
  • uterus

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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