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

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 hCG beta with healthy controls. Bladder biopsies of BPS/IC (CLSM: n = 10; qPCR: n = 15); Tumour-free control tissue from cystectomies (n = 12). hCG alpha, hCG beta and LHR expression were examined by confocal laser scanning microscopy (CLSM), and hCG beta expression was quantified. hCG beta 5 and hCG beta 7 mRNA splice variants were quantified in real-time polymerase chain reaction. We found constitutive expression of hCG alpha, hCG beta and LHR in healthy controls. HCG beta was significantly upregulated in BPS/IC patients in CLSM. PCR analysis revealed higher levels of hCG beta 7 than hCG beta 5 in controls and BPS/IC patients. 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 hCG beta is upregulated in BPS/IC urothelium and that hCG beta 7 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.