Enhanced urothelial expression of human chorionic gonadotropin beta (hCGβ) in bladder pain syndrome/interstitial cystitis (BPS/IC)

World J Urol. 2012 Jun;30(3):411-7. doi: 10.1007/s00345-011-0755-3. Epub 2011 Aug 30.

Abstract

Purpose: 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.

MeSH terms

  • Aged
  • Biomarkers / metabolism
  • Biopsy
  • Case-Control Studies
  • Chorionic Gonadotropin, beta Subunit, Human / metabolism*
  • Cystitis, Interstitial / metabolism*
  • Cystitis, Interstitial / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Receptors, LH / metabolism
  • Up-Regulation / physiology*
  • Urinary Bladder / metabolism
  • Urinary Bladder / pathology
  • Urothelium / metabolism*
  • Urothelium / pathology

Substances

  • Biomarkers
  • Chorionic Gonadotropin, beta Subunit, Human
  • Receptors, LH