AGE-RELATED INCREASE IN AN ADVANCED GLYCATION END-PRODUCT IN PENILE TISSUE - POTENTIAL ROLE IN ERECTILE DYSFUNCTION

Nonenzymatic glycosylation (glycation) of proteins, often referred to as the Maillard reaction, has been proposed to play a role in age and diabetes-related processes by forming protein and DNA adducts and cros slinks. These cross-links may contribute to erectile dysfunction by sc avenging nitric oxide, which is needed for erection. As the basis for a possible role of the advanced Maillard reaction in age-related erect ile dysfunction, we investigated the presence of the specific advanced glycation endproduct (AGE) pentosidine in penile corpus cavernosum ti ssue and penile tunica albuginea tissue as a function of age. A total of 23 penile tissue specimens were obtained at autopsy, from which 19 samples of tunica albuginea and 21 samples of corpus cavernosum were d erived. In addition, 13 penile corporal and tunical specimens were pro cured at the time of insertion of a penile prosthesis, from which 12 t unica albugineal specimens and 10 samples of corpus cavernosum were de rived. Collagen was extracted with acetic acid and pepsin digestion, a nd the final insoluble collagen product was acid-hydrolyzed with 6 N H CL for 24 h at 110 degrees C. Pentosidine was quantified by high-perfo rmance liquid chromatography using a reverse-phase column. The level o f pentosidine (expressed in picomoles per milligram of insoluble colla gen) was found to increase with age in cadaver as well as living penil e corporal and tunical albugineal tissues. Best-fit analysis revealed an exponential increase in both types of cadaver penile tissue, with r egression equations of y = 15.29 x 10((9.9e-3x)) R(2) = 0.79, being ob tained in the tunica-and y = 13.2 x 10((7.63e-3x)), R(2) = 0.56, in th e corpora. These correspond to 6- and 4-fold increases in pentosidine levels from puberty to the age of 100 years (P < 0.05), respectively. Mean pentosidine levels were higher in the tunica than in the corpora. Comparison of pentosidine levels in the tunica versus the corpora rev ealed a weakly linear correlation (y = 24.88 + 1.08x, R(2) = 0.32). Le vels in the tunical and corporal specimens from the living human speci mens fell with the predicted confidence intervals of the cadaveric tis sue. Tunical specimens from patients who underwent repair or revision of a previously inserted penile prosthesis had very low levels of pent osidine. The exponential age-related increase in pentosidine observed in both types of penile tissue suggests and im pairment of collagen tu rnover, which could be related to the advanced glycation reaction in a ging. It is not known whether pentosidine itself is directly associate d with erectile dysfunction, but its formation is usually accompanied by extensive tissue modification. Formation of advanced Maillard react ion products, which is greatly accelerated in aging, diabetes, and ure mia, could contribute to erectile dysfunction in these syndromes.