Olfactory receptors (ORs) are expressed not only in the sensory neurons of the olfactory epithelium, where they detect volatile substances, but also in various other tissues where their potential functions are largely unknown. Here, we report the physiological characterization of human OR51E2, also named prostate-specific G-protein-coupled receptor (PSGR) due to its reported up-regulation in prostate cancer. We identified androstenone derivatives as ligands for the recombinant receptor. PSGR can also be activated with the odorant ␤-ionone. Activation of the endogenous receptor in prostate cancer cells by the identified ligands evoked an intracellular Ca 2؉ increase. Exposure to ␤-ionone resulted in the activation of members of the MAPK family and inhibition of cell proliferation. Our data give support to the hypothesis that because PSGR signaling could reduce growth of prostate cancer cells, specific receptor ligands might therefore be potential candidates for prostate cancer treatment.Excessive signaling by G-protein-coupled receptors (GPCRs) 3 such as endothelin A receptor (1), bradykinin 1 receptor (2), follicle-stimulating hormone receptor (3), and thrombin receptor (4, 5) is known to occur in prostate cancers due to strong overexpression of the respective receptors. Activation of some of these GPCRs results in androgen-independent androgen receptor activation, thus promoting the transition of prostate cancer cells from an androgen-dependent to an androgen-independent state (6, 7).The prostate-specific G-protein-coupled receptor (PSGR) is a class A GPCR that was initially identified as a prostate-specific tumor biomarker (8 -10). It is specifically expressed in prostate epithelial cells, and its expression increases significantly in human prostate intraepithelial neoplasia and prostate tumors, suggesting that PSGR may play an important role in early prostate cancer development and progression (9, 11). Although expression of the human PSGR was found to be prostate-specific (10, 12), mRNA can also be detected in the olfactory zone and the medulla oblongata of the human brain (12). Human PSGR shares 93% amino acid homology to the respective mouse and rat homologues, which are also expressed in the brain (12). Interestingly, PSGR has numerous sequence motifs in common with the large superfamily of olfactory receptors (ORs), which build the largest class of human GPCRs and allow the recognition of a wide range of structurally diverse molecules in the nasal epithelium (13-15). Recently, also the steroid hormones androstenone and androstadienone were identified as OR ligands (16). In addition to their role in the sensory neurons of the nose, ORs have been found in different tissues throughout the body (17,18). Their function(s) in these extranasal locations are questionable except for in a few cases where functional studies have been performed in spermatozoa (19,20) and in enterochromaffin cells of the gastrointestinal tract (21).Here, we report the identification of steroid ligands of heterologously expressed PSGR...

3 5 9What ' s known on the subject? and What does the study add? Fournier ' s gangrene (FG) is a rare but life-threatening disease challenging the treating medical staff. Despite the fact that antibiotic therapy combined with surgery and intensive care surveillance are performed as standard treatment, mortality rates remain high. There have been efforts to develop a reliable tool to predict severity of the disease, not only to identify patients at highest risk of major complications or death but also to provide a target for medical teams and researchers aiming to improve outcome and to gather information for counselling patients. Laor et al . published the FG severity index (FGSI) in 1995 presenting a complex prediction score solely for patients with FG. Fifteen years later, Yilmazlar et al . suggested a new and supposedly more powerful scoring system, the Uludag FGSI (UFGSI), adding an age score and an extent of disease score to the FGSI.In the present study population we applied two scoring systems for outcome prediction that are solitarily applicable in patients with FG (FGSI, UFGSI), as well as two general scoring systems such as the established age-adjusted Charlson Comorbidity Index (ACCI) and the recently introduced surgical Apgar Score (sAPGAR) to compare them and to test whether one system might be superior to the other. In addition, we identifi ed potential prognostic factors in the study population. By contrast to many earlier studies, we performed a combined prospective and retrospective analysis and provided a 30-day follow up. In the cohort of the present study, older patients with comorbidities as well as a need for mechanical ventilation and blood transfusion are at higher risk of lethal outcome. All scores are useful to predict mortality. Despite including more variables, the UFGSI does not seem to be more powerful than the FGSI. In daily routine we suggest applying ACCI and sAPGAR, as they are more easily calculated, generally applicable and well validated. OBJECTIVE PATIENTS AND METHODS• In all, 44 patients were analysed. The scores were applied.• A Mann -Whitney U -test, Fisher ' s exact test, receiver operator characteristic (ROC) analysis and Pearson correlation analysis were performed. RESULTS• The results of the present study show a signifi cant association among FGSI ( P = 0.002), UFGSI ( P = 0.002), ACCI ( P = 0.004), sAPGAR ( P = 0.018) and death.• The differences between the area under the receiver operating characteristic curve of the scores were not signifi cant.• Non-survivors were older ( P = 0.046), had a greater incidence of acute renal failure ( P < 0.001) and coagulopathy ( P = 0.041), were treated more often with mechanical ventilation ( P = 0.001) and received more packed red blood cells (RBCs; P = 0.001). CONCLUSION• Older patients with comorbidities and need for mechanical ventilation and RBCs are at higher risk for death.• In the present cohort, scores calculated easily at the bedside, such as ACCI and sAPGAR, seemed to be as good at predicting outcome in patients with F...

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