Growth hormone (GH) receptors in prostate cancer: gene expression in human tissues and cell lines and characterization, GH signaling and androgen receptor regulation in LNCaP cells.

Various hormones and growth factors have been implicated in progression of prostate cancer, but their role and the underlying molecular mechanism(s) involved remain poorly understood. In this study, we investigated the role of human growth hormone (GH) and its receptor (GHR) in human prostate cancer. We first demonstrated mRNA expression of GHR and of its exon 9-truncated isoform (GHR(tr)) in benign prostate hyperplasia (BPH) and prostate adenocarcinoma patient tissues, as well as in LNCaP, PC3 and DU145 human prostate cancer cell lines. GHR mRNA levels were 80% higher and GHR(tr) only 25% higher, in the carcinoma tissues than in BPH. Both isoforms were also expressed in LNCaP and PC3 cell lines and somewhat less so in DU145 cells. The LNCaP cell GHR protein was further characterized, on the basis of its M(r) of 120kDa, its binding to two different GHR monoclonal antibodies, its high affinity and purely somatogenic binding to (125)I-hGH and its ability to secrete GH binding protein, all characteristic of a functional GHR. Furthermore, GH induced rapid, time- and dose-dependent signaling events in LNCaP cells, including phosphorylation of JAK2 tyrosine kinase, of GHR itself and of STAT5A (JAK2-STAT5A pathway), of p42/p44 MAPK and of Akt/PKB. No effect of GH (72h) could be shown on basal or androgen-induced LNCaP cell proliferation nor on PSA secretion. Interestingly, however, GH caused a rapid (2-12h) though transient striking increase in immunoreactive androgen receptor (AR) levels (< or =5-fold), followed by a slower (24-48h) reduction (< or = 80%), with only modest parallel changes in serine-phosphorylated AR. In conclusion, the GH-induced activation of signaling pathways, its effects on AR protein in LNCaP cells and the isoform-specific regulation of GHR in prostate cancer patient tissues, suggest that GH, most likely in concert with other hormones and growth factors, may play an important role in progression of human prostate cancer.

Tramadol improves patients' tolerance of transrectal ultrasound-guided prostate biopsy.

OBJECTIVES: To evaluate the analgesic advantage of tramadol in patients undergoing transrectal biopsy of the prostate in ambulatory settings compared with topical analgesia. METHODS: A total of 77 patients scheduled for prostate biopsy were randomly assigned to receive 5% lidocaine ointment 5 mL per rectum 10 minutes before the procedure (group 1) or lidocaine ointment combined with tramadol drops 1 mg/kg per os 40 minutes before the procedure (group 2). Pain severity, main cardiorespiratory parameters, difficulty of the procedure, procedure-related side effects, and complications were analyzed. RESULTS: No significant respiratory or hemodynamic disturbances were observed. The pain severity, as measured on a visual analog scale, was significantly lower in group 2 (P = 0.038), and the rate of overall satisfaction with the level of analgesia was significantly greater (P = 0.027). The urologist's assessment of "very easy" was assigned to 77.1% of procedures in group 2 compared with 54.8% of procedures in group 1 (P = 0.04). The rate of side effects in both groups was similar at 9.5% versus 11.4% (P = 0.785). CONCLUSIONS: The combination of lidocaine per rectum with tramadol per os is a simple and safe technique providing good analgesic effect and, therefore, can be recommended for transrectal ultrasound-guided prostate biopsy.