U. Schwarzer

OBJECTIVES: To determine the prevalence of Peyronie's disease, a localized connective tissue disorder of the penile tunica albuginea, the symptoms of which include palpable plaque, painful erections and curvature of the penis, in a large sample of men in Germany. SUBJECTS AND METHODS: A standardized questionnaire was sent to 8000 male inhabitants (age range 30-80 years) of the greater Cologne area (approximately 1.5 million inhabitants). Three questions about the self-diagnosis of Peyronie's disease were previously assessed for validity on 158 healthy men and 24 patients with confirmed Peyronie's disease. To optimize the response rate, the questionnaire was mailed three times to all the men. RESULTS: The response rate after the third mailing was 55.4% (4432 men): 142 men (3.2%, mean age 57.4 years, SD 13.4) reported the new appearance of a palpable plaque which, from the previous validation, was the most sensitive question and the main symptom of the disease. In men aged 30-39 years only 1.5% reported localized penile induration, compared with 3.0% in those 40-49 and 50-59 years, 4.0% in those 60-69 years and 6.5% of those > 70 years old. Newly occurring angulation was reported by 119 of the 142 men (84%) and painful erection by 66 (46.5%). The combination of the three symptoms (plaque, deviation and painful erection) was reported by 46 of the 4432 respondents (1.04%), i.e. 32% of the 142 men with penile induration; 58 of the 142 men (41%) reported erectile dysfunction. CONCLUSIONS: This is the first large cross-sectional, community-based study to examine the prevalence of Peyronie's disease. Using previously validated questions the prevalence of Peyronie's disease in the sample was 3.2%; this is much higher than indicated in previous reports. A comparably high prevalence is reported for diabetes and urolithiasis, suggesting that this 'rare' disease is more widespread than previously thought.

BACKGROUND: Testicular peritubular cells form an ill-characterized cellular compartment of the human testis, which forms a border with Sertoli cells and spermatogonial stem cells (SSCs). A recently developed culture method has identified parts of the secretory repertoire of human testicular peritubular cells (HTPCs), which includes nerve growth factor. Whether peritubular cells produce glial cell line-derived neurotrophic factor (GDNF) and may thus contribute to the stem cell niche is not known. METHODS: We studied GDNF production in isolated peritubular cells from men with normal spermatogenesis (HTPCs) and impaired spermatogenesis and testicular fibrosis (HTPC-Fs). Human testicular biopsies and peritubular cells in culture were evaluated using immunohistochemistry, laser microdissection (LMD), RT-PCR and measurement of GDNF and cAMP by enzyme-linked immunosorbent assay. We also tested whether GDNF production is regulated by tumour necrosis factor-alpha (TNF-alpha) or tryptase, the products of mast cells or macrophages. RESULTS: Peritubular wall cells are in close proximity to cells expressing the GDNF family co-receptor-alpha1. GDNF mRNA was detected in LMD samples of the peritubular and tubular but not interstitial compartments. HTPCs and HTPC-Fs lack FSH- and LH-receptors but express receptors for TNF-alpha and tryptase. Importantly, peritubular cells express GDNF and constitutively released GDNF into the medium in comparably high amounts. TNF-alpha and tryptase had no effect on the secretion of GDNF by HTPCs or HTPC-Fs. CONCLUSIONS: Peritubular cells in testes of normal and sub-/infertile men produce GDNF and are likely constitutive contributors of the SSC niche in the human testis.

Cyclists often complain of genital numbness and even of impotence. The purpose of this study was to determine if perineal compression during cycling causes changes in the penile blood supply, impotence and penile numbness. Forty healthy athletic men with a mean age of 30 +/- 5.3 years took part in the study. Transcutaneous penile oxygen pressure was obtained using a device consisting of a modified Clark pO2 electrode, attached to the glans of the penis. All men were measured in a standing position before, in a seated and standing position during and in a standing position after cycling. Additionally, a detailed interview was carried out with each man. The penile blood supply--which correlates with the transcutaneous PO2 at the glans-- decreased significantly in over 70% of the test subjects during cycling in a seated position. Cycling in a standing position did not show any alteration in the penile blood supply as compared to the values measured before exercising. Numbness of the genital region was reported by 61% of the cyclists. 19% of cyclists who had a weekly training distance of more than 400 km complained of erectile dysfunction. The results of the present study showed that there is a deficiency in penile perfusion due to perineal arterial compression. This could be a reason for penile numbness and impotence in long-distance cyclists. Therefore, we suggest restricting the training distance, and taking sufficient pauses during the course of prolonged and vigorous bicycle riding, in order to avoid penile numbness and impotence.

The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2) implies formation of prostaglandins (PGs). When screening different PGs for their ability to target human testicular peritubular cells (HTPCs), only a PG metabolite, 15-deoxy-Delta(12-14)-prostaglandin-J2 (15dPGJ2), was effective. In primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner. Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers were unchanged. Collagen gel contraction assays revealed that this loss correlates with a reduced ability to contract. Experiments with an antagonist (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2 receptor (i.e. peroxisome proliferator-activated receptor-gamma) indicated that peroxisome proliferator-activated receptor-gamma is not directly involved. Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The antioxidant N-acetylcysteine not only blocked ROS formation but also prevented the increase in cell size and the loss of contractility in HTPCs challenged with 15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC phenotype and contractility of human peritubular cells and possibly is involved in the development of human male sub-/infertility.