title: Estrogen and progesterone play pivotal roles in endothelial progenitor cell proliferation.
abstract: BACKGROUND
  It has been previously suggested that angiogenesis occurs during the menstrual cycle. Moreover, a rise in uterine blood flow is largely maintained by vasodilatation and substantial increases in angiogenesis. It is known that estradiol (E2) and progesterone (P4) are involved in angiogenesis. Recently, endothelial progenitor cells (EPCs) were found to be involved in neovascularization; however, their roles in uterine neovascularization have not been well characterized. We hypothesized that E2- or P4-mediated EPC proliferation plays important roles in uterine neovascularization during the menstrual cycle.
  
  
  METHODS
  The number of EPCs in peripheral blood from subjects in the menstrual phase (n=12), follicular phase (n=8), and luteal phase (n=16), was measured using flow cytometry. Peripheral blood mononuclear cells (PBMCs) were cultured for seven days with or without 17beta-estradiol (E2beta) or P4, followed by assessment of EPC proliferation based upon the uptake of acetylated low density lipoprotein (LDL) and lectin. The expression of estrogen receptor (ER) or progesterone receptor (PR) in EPCs was also evaluated using real-time PCR.
  
  
  RESULTS
  E2beta and P4 significantly increased the proliferation of EPCs derived from the peripheral blood of subjects in menstrual phase, but not subjects in the luteal phase. In addition, the expression level of ERalpha was markedly higher than ERbeta in EPCs derived from women in menstrual phase.
  
  
  CONCLUSIONS
  EPC proliferation is induced during the menstrual phase and proliferation can be affected by estrogen through ERalpha activation.
authors.affiliation: Department of Obstetrics and Gynecology, Ehime Prefectural Niihama Hospital, Hongo, Niihama, Ehime, 792-0042 Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Keiichi
authors.initials: K
authors.lastname: Matsubara
mesh_terms: D000328:Adult; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D047629:Estrogen Receptor beta / Q000096:biosynthesis; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D008183:Luteal Phase / Q000097:blood; D008597:Menstrual Cycle / Q000187:drug effects / Q000502:physiology*; D015735:Mifepristone / Q000494:pharmacology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D011374:Progesterone / Q000494:pharmacology*; D013234:Stem Cells / Q000502:physiology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol