title: Remodeling of estrogen-dependent sympathetic nerve fibers seems to be disturbed in adenomyosis.
abstract: OBJECTIVE
  To investigate neuronal remodeling processes in the uterine innervation, particularly a remodeling of sympathetic nerve fibers, as well as the role of estrogen in this modulation in adenomyosis.
  
  
  METHODS
  Retrospective case-control study.
  
  
  METHODS
  University hospital endometriosis center.
  
  
  METHODS
  Forty-two patients with histologically proven adenomyosis and 19 patients without adenomyosis.
  
  
  METHODS
  Endometrial and myometrial tissue were immunohistochemically analyzed to further characterize the uterine innervation.
  
  
  METHODS
  Immunohistochemical analysis was used to identify PGP 9.5-, substance P-, and tyrosine hydroxylase-positive nerve fibers. The expression of the aromatase cytochrome P450 was evaluated in uterine tissue, and the expression of the estrogen receptor (ER) -α and ERβ in uterine nerve fibers was analyzed.
  
  
  RESULTS
  Adenomyotic lesions are not innervated. The density of sympathetic nerve fibers in the myometrium of women with adenomyosis is reduced when compared with the nonadenomyosis group. The aromatase expression in the myometrium of women with adenomyosis was increased when compared with the control group. The ERα/ERβ ratio is in trend shifted to the ERα side in the myometrial tyrosine hydroxylase-positive nerve fibers in adenomyosis compared to the controls.
  
  
  CONCLUSIONS
  The disruption of the modulation of the uterine sympathetic innervation seems to be an important aspect in the pathogenesis of adenomyosis. Estrogen and its receptors seem to play a crucial role in the depletion of myometrial sympathetic nerve fibers.
authors.affiliation: Endometriosis Research Centre Charité, Department of Gynaecology, Charité, Campus Benjamin Franklin, Berlin, Germany. maria-luisa.barcena-de-arellano@charite.de
authors.forename: Maria L
authors.initials: ML
authors.lastname: Barcena de Arellano
authors.forename: Jeannette
authors.initials: J
authors.lastname: Oldeweme
authors.forename: Julia
authors.initials: J
authors.lastname: Arnold
authors.forename: Achim
authors.initials: A
authors.lastname: Schneider
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mechsner
mesh_terms: D062788:Adenomyosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D000320:Adrenergic Fibers / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D000328:Adult; D001141:Aromatase / Q000378:metabolism; D016022:Case-Control Studies; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D020073:Gravidity / Q000502:physiology; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D008875:Middle Aged; D009416:Nerve Regeneration / Q000187:drug effects; D010298:Parity / Q000502:physiology; D011247:Pregnancy; D012189:Retrospective Studies; D014599:Uterus / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism / Q000503:physiopathology
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D001141:Aromatase
keywords: Adenomyosis; aromatase; estrogen; estrogen-dependent remodeling; sympathetic innervation