title: Estrogen metabolites in human corpus luteum physiology: differential effects on angiogenic activity.
abstract: To determine tissue concentrations of E2, estrone, P, and estrogens metabolites (EMs) 2-methoxyestradiol, 2-methoxyestrone, 4-hydroxyestrone, and 16-ketoestradiol in corpus luteum (CL) of different ages, and after hCG administration; and to examine the effects of EMs on vascular endothelial growth factor (VEGF) secretion and angiogenic activity released by cultured luteinizing granulosa cells in the presence and absence of hCG.
  
  
  
  Experimental study.
  
  
  
  University.
  
  
  
  Thirty-two healthy women of reproductive age.
  
  
  
  Corpus luteum was collected at the time of minilaparotomy for tubal sterilization, at varying stages of the luteal phase (LP). Late-LP CL was collected 24 hours after IM administration of 10,000 IU hCG. Granulosa cells were isolated from follicular aspirates obtained from healthy women participating in our IVF program for male factor infertility.
  
  
  
  Estrogen metabolite concentrations were determined in CL tissue, and VEGF was assessed in conditioned medium. The angiogenic activity was analyzed by bioassay.
  
  
  
  Concentrations of EMs with proangiogenic activity (16-ketoestradiol and 4-hydroxyestrone) were higher in early and mid-LP CL vs. late-LP CL. These EMs and hCG increased VEGF production and angiogenic activity. Conversely, late-LP CL had significantly higher levels of 2-methoxyestrone and 2-methoxyestradiol, which have antiangiogenic activity. Administration of hCG reduced the production of these EMs.
  
  
  
  Our findings suggest that the EMs are important paracrine modulators of CL function. Administration of hCG increases the production of EMs with proangiogenic activity and reduces the secretion of those EMs with antiangiogenic action, suggesting a novel mechanism by which the late-LP CL is rescued in conception cycles.
authors.affiliation: Institute for Maternal and Child Research, Santiago, Chile.
authors.forename: Soledad
authors.initials: S
authors.lastname: Henríquez
authors.affiliation: Institute for Maternal and Child Research, Santiago, Chile.
authors.forename: Paulina
authors.initials: P
authors.lastname: Kohen
authors.affiliation: Research Technology Program, Biomedical Research (formerly SAIC-Frederick), Frederick National Laboratory for Cancer Research, Frederick, Maryland.
authors.forename: Xia
authors.initials: X
authors.lastname: Xu
authors.affiliation: Maranatha Baptist University, Watertown, Wisconsin.
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Veenstra
authors.affiliation: Institute for Maternal and Child Research, Santiago, Chile.
authors.forename: Alex
authors.initials: A
authors.lastname: Muñoz
authors.affiliation: Institute for Maternal and Child Research, Santiago, Chile; Department of Obstetrics and Gynecology, Faculty of Medicine, San Borja-Arriaran Clinical Hospital, University of Chile, Santiago, Chile.
authors.forename: Wilder A
authors.initials: WA
authors.lastname: Palomino
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Virginia Commonwealth University, Richmond, Virginia.
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
authors.affiliation: Institute for Maternal and Child Research, Santiago, Chile; Department of Obstetrics and Gynecology, Faculty of Medicine, San Borja-Arriaran Clinical Hospital, University of Chile, Santiago, Chile. Electronic address: ldevoto@med.uchile.cl.
authors.forename: Luigi
authors.initials: L
authors.lastname: Devoto
mesh_terms: D000077584:2-Methoxyestradiol; D001711:Biotransformation; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003338:Corpus Luteum / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D004970:Estrone / Q000378:metabolism; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D006894:Hydroxyestrones / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011374:Progesterone / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D006063:Chorionic Gonadotropin; D004967:Estrogens; D006894:Hydroxyestrones; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004970:Estrone; C026418:4-hydroxyestrone; D011374:Progesterone; D004958:Estradiol; C003599:16-ketoestradiol; D000077584:2-Methoxyestradiol; C003655:2-methoxyestrone
keywords: 16-ketoestradiol; 2-Methoxyestradiol; 2-methoxyestrone; 4-hydroxyestrone; human corpora lutea