title: Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC).
abstract: OBJECTIVE
  Bladder pain syndrome/interstitial cystitis (BPS/IC) is associated with urothelial lesions. Pathomechanisms of urothelial damage and factors for urothelial restoration are unknown. hCG is a factor for cellular differentiation, angiogenesis and immune competence of the endometrium during pregnancy. Clinical observations demonstrate improvement of BPS/IC symptoms during pregnancy or during infertility treatment with hCG. Our research aims were to examine the expression of hCG and luteinizing hormone receptor (LHR) in the urothelium of BPS/IC patients and compare the levels of hCGβ with healthy controls.
  
  
  METHODS
  Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCGα, hCGβ and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCGβ expression was quantified. hCGβ5 and hCGβ7 mRNA splice variants were quantified in real-time polymerase chain reaction.
  
  
  RESULTS
  We found constitutive expression of hCGα, hCGβ and LHR in healthy controls. HCGβ was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCGβ7 than hCGβ5 in controls and BPS/IC patients.
  
  
  CONCLUSIONS
  The constitutive expression of hCG and LHR speaks in favour for a functional signalling in urothelial cells without any association with either pregnancy or tumour. We show for the first time that hCGβ is upregulated in BPS/IC urothelium and that hCGβ7 is the dominant splice variant in those cells. Our findings imply a major role of hCG for urothelial integrity and a disturbance of hCG signalling in case of BPS/IC. We conclude that hCG could gain therapeutical relevance in the future.
authors.affiliation: Department of Urology, University Hospital Leipzig, Liebigstr. 20, 04103, Leipzig, Germany. thilo.schwalenberg@uniklinik-leipzig.de
authors.forename: Thilo
authors.initials: T
authors.lastname: Schwalenberg
authors.forename: Jens-Uwe
authors.initials: JU
authors.lastname: Stolzenburg
authors.forename: Thi Phuc
authors.initials: TP
authors.lastname: Ho
authors.forename: Tobias
authors.initials: T
authors.lastname: Mallock
authors.forename: Siegurd
authors.initials: S
authors.lastname: Hartenstein
authors.forename: Henry
authors.initials: H
authors.lastname: Alexander
authors.forename: Gerolf
authors.initials: G
authors.lastname: Zimmermann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Hohenfellner
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
authors.forename: Lars-Christian
authors.initials: LC
authors.lastname: Horn
authors.forename: Jochen
authors.initials: J
authors.lastname: Neuhaus
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016022:Case-Control Studies; D018997:Chorionic Gonadotropin, beta Subunit, Human / Q000378:metabolism*; D018856:Cystitis, Interstitial / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011974:Receptors, LH / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000378:metabolism* / Q000473:pathology
chemical_list: D015415:Biomarkers; D018997:Chorionic Gonadotropin, beta Subunit, Human; D011974:Receptors, LH