Band 22, Heft 3

Purpose: To compare histological features of prostate cancer according to both obesity, defined by a body mass index (BMI) ≥30 kg/m 2 , and androgenic status in patients who underwent radical prostatectomy. Materials and methods: Between March 2007 and September 2013, clinical, pathological and biological data were prospectively collected for patients referred for radical prostatectomy in a single European center. Preoperative total testosterone (TT) and bioavailable testosterone (bioT) serum determinations were performed. The threshold for hypogonadism was set at TT <3 ng/mL. The preoperative PSA value was registered. Gleason score (GS) and predominant Gleason pattern (PrdGP) were determined in prostate tissue specimens, and crosschecked by two uro-pathologists. Statistical analyzes were done for PrdGP4 risk assessment. Results: A total of 937 consecutive patients were included. One hundred and thirty-five filled the criterion for obesity (14.4%), out of which 42 had TT <3 ng/mL (31.1%), while in non-obese patients, only 97 had TT <3 ng/mL (12.0%). In prostate specimens, mean GS was 6.8±0.5: 291 patients (31.1%) had a PrdGP4. The incidence of PrdGP4 was higher (p<0.001) in the 135 obese patients [50% when hypogonadal (p<0.02) or 42% when eugonadal (p<0.005)] than in non-obese patients (28.9% and 27.1%, respectively). In multivariable analyzis for PrdGP4 risk, obesity, TT <3 ng/mL, PSA, and age were independent risk factors. Conclusions: Both obesity and hypogonadism are independent risk factors for PrdGP4 in patients who underwent radical prostatectomy and should be taken into account in localized prostate cancer management, to improve the therapeutic choice, especially when prostate sparing approach is considered.

Background : Crohn’s disease is an inflammatory chronic bowel disease characterized by an imbalanced production of pro-inflammatory mediators (tumor necrosis factor-α) and an increased recruitment of leukocytes to the site of inflammation. Low serum testosterone is associated with an increase in inflammatory factors, while testosterone administration reduces them. There is evidence for an immunomodulatory effect of testosterone on differentiation of regulatory T cells. Materials and methods : The research was carried out in clinics in Germany and Syria. The study was a cumulative, prospective, registry study with an increasing number of men over time receiving testosterone. While men diagnosed with Crohn’s disease received appropriate treatment for Crohn’s disease, they were tested for testosterone deficiency (cut-off point ≤12.1 nmol/L). In total, 92 men received parenteral testosterone undecanoate 1000 mg/12 weeks for up to 7 years. Fourteen men opted not to receive testosterone and served as a comparison group. Results : In men receiving testosterone, the Crohn’s Disease Activity Index declined from 239.36±36.96 to 71.67±3.26 at 84 months (p<0.0001 vs. baseline). C-reactive protein levels decreased from 12.89±8.64 to 1.78±1.37 mg/L at 84 months (p<0.0001 vs. baseline). Leukocyte count decreased from 11.93±2.85 to 6.21±1.01×10 9 /L (p<0.0001 at 84 months vs. baseline). No changes were observed in the comparison group. There were no significant side effects of testosterone. Conclusions : Normalizing serum testosterone in hypogonadal men with Crohn’s disease had a positive effect on the clinical course, also evidenced by biochemical parameters. Testosterone administration appeared safe.

Background : Gonadotropin-regulated testicular RNA helicase (GRTH) is a testis-specific member of the DEAD-box family of RNA helicases present in Leydig and germ cells. It is a transport protein of mRNAs from nucleus to cytoplasmic sites and is essential for posttranscriptional regulation and completion of spermatogenesis. Transition protein 2 (Tp2), which associates with GRTH and is required for spermatid elongation, failed to express in GRTH null mice with impaired mRNA nuclear export. The present study determines GRTH binding motifs/regions that associate with Tp2 mRNA transcripts. Materials and methods : RNA-protein interaction was analyzed using biotin-labeled electrophoretic mobility gel shift assays (EMSA). 3′-biotin-labeled RNA (Tp2) was incubated with mGRTH protein (full length/sequential deletion of specific and conserved RNA helicase motifs of GRTH) expressed from in vitro TNT coupled reticulocyte lysate system. Binding specificity was further elucidated by mutagenesis and antibody supershift analysis. Results : RNA-EMSA revealed that the 3′ UTR of Tp2 RNA (127 nt from TGA) was retarded in presence of full length GRTH. Nucleotide sequences downstream of TGA of the Tp2 transcript (1–47 and 78–127 nt) are important for binding to GRTH. Sequential deletions/point mutations in GRTH revealed region(s) of conserved binding motifs of RNA helicases (Ia and V) essential for GRTH binding to Tp2 mRNA. Conclusions: Our studies provide insights into the association of Tp2 expression via binding to the conserved RNA binding motifs of GRTH protein and the basis for understanding GRTH in the regulation of the genes essential for germ cell elongation and completion of spermatogenesis.