Regional differences in the extracellular matrix of the human spongy urethra as evidenced by the composition of glycosaminoglycans

Purpose: Despite the concept that the spongy urethra is a unique entity clinical evidence suggests the existence of segmental structural differences. The spongy urethra has a vascular nature, its cells may express different phenotypes and the extracellular matrix that they synthesize should reflect these differences. Glycosaminoglycans are components of the extracellular matrix that have key roles in the normal physiology and pathology of several tissues. Although total collagen content of the urethra was determined, we also analyzed urethral glycosaminoglycans (GAGS). Materials and Methods: Fresh, macroscopically normal cadaveric urethral samples were obtained from 15 men who died at a mean age of 25.4 years. The urethra was divided into glanular, penile and bulbar segments, which were then analyzed separately. Total GAG concentration was assessed by hexuronic acid assay and expressed as jig. hexuronic acid per mg. dry tissue, while the proportions of sulfated GAGs were determined by agarose gel electrophoresis. Hyaluronan concentration was determined by ion exchange chromatography and total tissue collagen was estimated as hydroxyproline content. Results: Total GAG concentration was heterogeneous along the spongy urethra (p <0.001). Mean values plus or minus standard deviation in the glanular, penile and bulbar segments were 2.53 +/- 0.42, 2.11 +/- 0.47 and 1.47 +/- 0.4 μg./mg., respectively. The most predominant GAG was hyaluronan and its highest mean concentration of 50.1% +/- 3.7% was found in the glanular urethra. The most predominant sulfated GAG in the male urethra was dermatan sulfate, followed by chondroitin sulfate and heparan sulfate. Total collagen content and the GAG-to-collagen ratio varied along the spongy urethra and were lowest in the bulbar segment. Conclusions: The extracellular matrix of the human spongy urethra shows regional differences, as evidenced by biochemical analysis of GAG and collagen. This heterogeneity implies functional adaptations in the various segments and may affect the physiology and segmental incidence of urethral diseases.