Estrogen selectively up-regulates eNOS and nNOS in reproductive arteries by transcriptional mechanisms

Charles R. Rosenfeld, Cui Chen, Tim Roy, Xiao Tie Liu

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


OBJECTIVE: To determine the mechanism(s) whereby daily and acute estradiol-17β (E2β) exposure modifies endothelium-derived nitric oxide synthase (eNOS) and vascular smooth muscle (VSM) neuronal nitric oxide synthase (nNOS) in reproductive and nonreproductive arteries and to localize NOS isoform expression within the vessel wall. METHODS: Oophorectomized nonpregnant ewes received E2β (1 μg/kg per day) or no E2β for 5-6 days or acute E2β (1 μg/kg) on day 6-7 with or without daily E2β. Uterine, mammary, mesenteric, and femoral arteries were collected at completion of each study, adventitia were removed, and samples were frozen and stored at -80C. After separating endothelium and VSM, NOS isoform mRNA was measured using reverse transcription-polymerase chain reaction. VSM nNOS protein was determined by Western analysis. RESULTS: Basal eNOS and nNOS mRNA was greatest (P < .02) in reproductive artery endothelium and VSM, respectively. Daily E2β was required for maximum uterine vascular responses to acute E2β and was associated with increased reproductive artery endothelial eNOS mRNA (>1.5-fold, P < .02) and uterine VSM nNOS mRNA (>2.5-fold, P < .003) and protein (21%, P < .05). Acute E2β in the presence and absence of daily E2β also increased uterine eNOS 68% and 28% (P = .01), respectively, within 90 minutes but did not affect VSM nNOS. Mammary eNOS increased 71% only after E2β withdrawal; VSM nNOS was unchanged. Neither NOS isoform was altered in nonreproductive arteries by daily or acute E2β. CONCLUSION: Basal eNOS and nNOS isoform expression is greatest in arteries from reproductive tissues, and isoform responses to E2β are cell specific and transcriptionally regulated. Furthermore, optimal uterine vascular responses to acute E2β exposure require daily E2β exposure that enhances basal NOS expression and abundance.

Original languageEnglish (US)
Pages (from-to)205-215
Number of pages11
JournalJournal of the Society for Gynecologic Investigation
Issue number4
StatePublished - May 2003


  • Endothelium
  • Mammary artery
  • Mesenteric artery
  • Uterine artery
  • Vascular smooth muscle

ASJC Scopus subject areas

  • Obstetrics and Gynecology


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