title: 2-Methoxyestradiol in the human corpus luteum throughout the luteal phase and its influence on lutein cell steroidogenesis and angiogenic activity.
abstract: OBJECTIVE
  To quantitate 2-methoxyestradiol (2-ME) in human corpus luteum (CL) of different ages and to determine the expression of cytochrome-P450-1A1 (CYP1A1) and catechol-O-methyl transferase (COMT) in CL and the action of 2-ME on P, vascular endothelial growth factor (VEGF) secretion, and luteal angiogenesis.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  University division of reproductive endocrinology.
  
  
  METHODS
  Twenty-four women of reproductive age.
  
  
  METHODS
  CL was collected from 15 women during the minilaparotomy for tubal sterilization. Granulosa lutein cells were harvested 36 hours after hCG administration in patients undergoing IVF.
  
  
  METHODS
  Levels of 2-ME were determined by high-performance liquid chromatography in CL. CYP1A1 and COMT were assessed by immunohistochemistry and Western blot. P and VEGF were measured by radioimmunoassay and ELISA. The angiogenic potential was analyzed using EA.hy926 cells.
  
  
  RESULTS
  Plasma levels of E₂ decreased in the late luteal phase in association with an increase in luteal tissue of 2-ME concentrations. Concomitantly, there was a significant reduction of angiogenic activity in late CL. There was no significant variation in CYP1A1 and COMT expression in all CL. In physiological doses, 2-ME inhibited basal VEGF by granulosa lutein cells and diminished the angiogenic activity in conditioned media but did not prevent P and VEGF production stimulated by hCG.
  
  
  CONCLUSIONS
  These data suggest the participation of 2-ME in physiological luteolysis by reducing angiogenesis. However, 2-ME did not prevent in vitro hCG stimulation of P biosynthesis, providing a mechanism for CL rescue in the cycle of conception.
authors: Institute for Maternal and Child Research (IDIMI), Faculty of Medicine, San Borja-Arriaran Clinical Hospital, University of Chile, Santiago, Chile.
authors: Paulina
authors: P
authors: Kohen
authors: Soledad
authors: S
authors: Henríquez
authors: Candy
authors: C
authors: Rojas
authors: Phillip M
authors: PM
authors: Gerk
authors: Wilder A
authors: WA
authors: Palomino
authors: Jerome F
authors: JF
authors: Strauss
authors: Luigi
authors: L
authors: Devoto
mesh_terms: D000077584:2-Methoxyestradiol; D000328:Adult; D002394:Catechol O-Methyltransferase / Q000378:metabolism; D002460:Cell Line; D003338:Corpus Luteum / Q000098:blood supply* / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D008184:Luteal Cells / Q000378:metabolism*; D008183:Luteal Phase / Q000097:blood / Q000378:metabolism*; D018919:Neovascularization, Physiologic; D011374:Progesterone / Q000096:biosynthesis*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone; D004958:Estradiol; D000077584:2-Methoxyestradiol; C569463:CYP1A1 protein, human; D019363:Cytochrome P-450 CYP1A1; D002394:Catechol O-Methyltransferase
keywords: 2-methoxyestradiol; angiogenic potential; human corpus luteum; vascular endothelial growth factor