title: Localization of TrkB and p75 receptors in peritoneal and deep infiltrating endometriosis: an immunohistochemical study.
abstract: BACKGROUND
  The roles of the neurotrophins NGF (Neurotrophic growth factor) and BDNF (brain-derived neurotrophic factor) in neuronal growth and development are already known. Meanwhile, the neurotrophin receptors TrkA (tropomyosin related kinase A), TrkB, and p75 are important for determining the fate of cells. In endometriosis, this complex system has not been fully elucidated yet. The aim of this study was to evaluate the expression and location of these neurotrophins and their receptors in peritoneal (PE) and deep infiltrating endometriotic (DIE) tissues and to measure and compare the density of nerve fibers in the disease subtypes.
  
  
  METHODS
  PE lesions (n = 20) and DIE lesions (n = 22) were immunostained and analyzed on serial slides with anti-BDNF, -NGF, -TrkA, -TrkB, -p75,-protein gene product 9.5 (PGP9.5, intact nerve fibers) and -tyrosine hydroxylase (TH, sympathetic nerve fibers) antibodies.
  
  
  RESULTS
  There was an equally high percentage (greater than 75 %) of BDNF-positive immunostaining cells in both PE and DIE. TrkB (major BDNF receptor) and p75 showed a higher percentage of immunostaining cells in DIE compared to in PE in stroma only (p < 0.014, p < 0.027, respectively). Both gland and stroma of DIE lesions had a lower percentage of NGF-positive immunostaining cells compared to those in PE lesions (p < 0.01 and p < 0.01, respectively), but there was no significant reduction in immunostaining of TrkA in DIE lesions. There was no difference in the mean density of nerve fibers stained with PGP9.5 between PE (26.27 ± 17.32) and DIE (28.19 ± 33.15, p = 0.8). When we performed sub-group analysis, the density of nerves was significantly higher in the bowel DIE (mean 57.33 ± 43.9) than in PE (mean 26.27 ± 17.32, p < 0.01) and non-bowel DIE (mean 14.6. ± 8.6 p < 0.002).
  
  
  CONCLUSIONS
  While the neurotrophin BDNF is equally present in PE and DIE, its receptors TrkB and p75 are more highly expressed in DIE and may have a potential role in the pathophysiology of DIE, especially in promotion of cell growth. BDNF has a stronger binding affinity than NGF to the p75 receptor, likely inducing sympathetic nerve axonal pruning in DIE, resulting in the lower nerve fiber density seen.
authors: Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria.|Department of Obstetrics and Gynecology, Gadjah Mada University, Yogyakarta, Indonesia.
authors: Agung
authors: A
authors: Dewanto
authors: Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Jozsef
authors: J
authors: Dudas
authors: Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Rudolf
authors: R
authors: Glueckert
authors: Endometriosis Centre Charité, Department of Gynecology - Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany.
authors: Sylvia
authors: S
authors: Mechsner
authors: Department of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Anneliese
authors: A
authors: Schrott-Fischer
authors: Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria.
authors: Ludwig
authors: L
authors: Wildt
authors: Department of Gynecological Endocrinology and Reproductive Medicine, Medical University of Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria. beata.seeber@i-med.ac.at.
authors: Beata
authors: http://orcid.org/0000-0002-8224-4126
authors: B
authors: Seeber
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000096:biosynthesis*; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis*; D008875:Middle Aged; D010537:Peritoneum / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D020800:Receptor, Nerve Growth Factor / Q000032:analysis / Q000096:biosynthesis*; D020813:Receptor, trkB
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D008562:Membrane Glycoproteins; D020800:Receptor, Nerve Growth Factor; C579455:BDNF protein, human; D011505:Protein-Tyrosine Kinases; D020813:Receptor, trkB; C000591259:tropomyosin-related kinase-B, human
keywords: BDNF; Endometriosis; Immunohistochemistry; Neurotrophins