Objective To cladfy the dependence of neural nitric oxide synthase mRNA (nNOSmRNA) and endothelial nitric oxide synthase mRNA (eNOSmRNA) on androgens (testosterone [T] and dihydrotestosterone [DHT]).Methods 160 male Sprague Dawley (SD) rats were divided into Groups A (56 rats, 5 weeks old), B (50rets,10 weeks old) and C (54 rats, 58 weeks old).Groups A, B and C were all subdivided respectively into five Subgroups. Subgroup 1: intact osntrels;Subgroup 2: castrated; Subgroup 3: castrated with testosterone ubdecanoate 25 mg/kg·mon-1,intramuscular injection, Subgroup 4: castrated with testosterone undecanoate 50 mg/kg·mon-1,intramuscular injection and Subgroup 5: treated with finaeteride 4.5 mg/kg·day-1, orally. Four and ten weeks after treatments described above, one half of the rats were killed. Serum samples were token for measurements of T, free testosterone (FT) and DHT by raclioimmunoassay. Penile samples were treated with liquid nitrogen and then stored at-80℃.nNOSmRNA and eNOSmRNA were detected by semiquantitative reveres-transcription polymerase chain reaction (RT-PCR) and Dot blot.Resulte There was no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 in all Groups A, B and C. The expression of penile eNOSmRNA of Group A was significantly increased (4 weeks model) (P＜0.05) or increased (10 weeks model) (P＞0.05) in Subgroup 2 or 5 compared with those in Subgroup 1.There wes no significant difference between Subgroup 1 and Subgroup 2 or Subgroup 5 of Group B in 4 weeks model (P＞0.05).There was an elevation when animals were castrated or treated with finasteride in the 10 weeks model.The expreseion of penile eNOSmRNA of Group C was significantly increased (10 weeks model) (P＜0.05)or increased (4 weeks model) in Subgroup 2 compared with those in Subgroup 1.The production of eNOSmRNA in Subgroup 5 was also increased (including 4- and 10-week models). When T was supplied for castration, the penile eNOSmRNA was desreased to some extent; the greater the dose of T given, the lower penile eNOSmRNA was observed.Conclusions The expression of eNOSmRNA in SD rat penile tissue increases while T or DHT diminishes.Sometimes androgens medaulate penile eNOSmRNA in opposite directions. There is no srrelation between theexpression of nNOSmRNA and androgens (including Tand DHT) . Androgens give rise to penile erectionprobably not via the NOS pathway.

芳香化酶(CYP19)基因变体同精子浓度和活性的关系

前列腺癌细胞中两个雄激素应答元件调节雄激素对MMP-2表达的调控

Aim:To characterize the matrix metalloproteinases (MMP)-2 promoter and to identify androgen response elements (AREs) involved in androgen-induced MMP-2 expression. Methods: MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction (RT-PCR). MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays (EMSA) were used to verify the identified AREs in the MMP-2 promoter. Results: Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1 591 to -1259 (relative to the start codon) of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5'-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor (AR) interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment.Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion: Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.

促黄体激素释放激素激动剂或抗雄激素单一疗法对老年男子局限性前列腺癌(T1-2)的长期疗效:回顾性研究

Aim: To evaluate the long-term effectiveness, side effects and compliance rates of two types of drugs (luteinizing hormone-releasing hormone [LHRH] agonist and antiandrogen) that were used individually to treat patients with localized prostate cancer (T1-2) at our institution. Methods: Ninety-seven patients who were diagnosed in the period from April 1997 to January 2000 as having clinically localized prostate cancer (T1-2) received either LHRH agonist (leuprolide acetate 7.5 mg/month) monotherapy (group 1, n = 62) or antiandrogen monotherapy (group 2, n = 35; 18received bicalutamide 50 mg q.d., 13 received nilutamide 150 mg t.I.d. And 4 received flutamide 250 mg t.I.d.). The mean age in both groups was 76 years. Results: The mean follow-up time was (50.8 ± 8.5) months in group 1 and (43.1 ± 2.2) months in group 2. Prostate-specific antigen (PSA) levels rose in only 1 of the 62 patients (1.6%) in group 1, and in 20 of the 35 patients (57.1%) in group 2. In group 2, 10 of the 20 patients (50 %) with increasing PSA levels were treated with LHRH salvage therapy, and eight (80%) responded. Hot flashes (54.8%) and lethargy (41.9%) were the most common side effects in group 1. In contrast, nipple-tenderness (40%) and light-dark adaptation (17.1%) were more often seen in group 2. Only 1 of the 62 patients (1.6%) in group 1 switched to another medication because of adverse side effects; whereas 8 of the 35 patients (22.9%) in group 2 did so. Conclusion: Unlike antiandrogen monotherapy, LHRH agonist monotherapy provided long-term durable control of localized prostate cancer (T1-2). It can also be an effective treatment option for patients whose disease failed to respond to antiandrogen monotherapy. The limitations of our study are the lack of health outcomes analysis and a small sample size.

MEISI作为潜在的雄激素受体负调控因子发挥功能