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In this study, we evaluated genetic variants of the androgen metabolism genes CYP17A1, CYP3A4, and CYP3A43 to determine whether they play a role in the development of prostate cancer (PCa) in Korean men. The study population included 240 pathologically diagnosed cases of PCa and 223 age-matched controls. Among the 789 single-nucleotide polymorphism (SNP) database variants detected, 129 were reported in two Asian groups (Han Chinese and Japanese) in the HapMap database. Only 21 polymorphisms of CYP17A1, CYP3A4, and CYP3A43 were selected based on linkage disequilibrium in Asians (r2 = 1), locations (SNPs in exons were preferred), and amino acid changes and were assessed. In addition, we performed haplotype analysis for the 21 SNPs in CYP17A1, CYP3A4, and CYP3A43 genes. To determine the association between genotype and haplotype distributions of patients and controls, logistic analyses were carried out, controlling for age. Twelve sequence variants and five major haplotypes were identified in CYP17A1. Five sequence variants and two major haplotypes were identified in CYP3A4. Four sequence variants and four major haplotypes were observed in CYP3A43. CYP17A1 haplotype-2 (Ht-2) (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.18) was associated with PCa susceptibility. CYP3A4 Ht-2 (OR: 1.87; 95% CI: 1.02-3.43) was associated with PCa metastatic potential according to tumor stage. rs17115149 (OR: 1.96; 95% CI: 1.04-3.68) and CYP17A1 Ht-4 (OR: 2.01; 95% CI: 1.07-4.11) showed a significant association with histologic aggressiveness according to Gleason score. Genetic variants of CYP17A1 and CYP3A4 may play a role in the development of PCa in Korean men.

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen (PSA) levels in healthy men with serum PSA level below 4 ng mL(-1). The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment (HOMA [fasting glucose x fasting insulin]/22.5) and quantitative insulin sensitivity check index (QUICKI; 1/[log (fasting insulin) + log (fasting glucose)]). Age-adjusted body mass index (BMI) was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance (ANOVA) test and Duncan's multiple comparison test (P < 0.001), but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI (P < 0.001). Age, BMI, insulin resistance by HOMA or QUICKI were significantly independent variables to serum PSA level in a multivariate linear regression analysis (P < 0.001). Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

Aim: To evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), and to investigate whether they are associated with the development and progression of PCa., Methods: Immunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups: localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index (BMI) and PCa., Results: The percentage of the leptin expression in PCa was significantly higher than that in BPH (P < 0.01). For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa (P < 0.05). Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa (Gleason score =or< 6) and poorly differentiated PCa (Gleason score 8?0) (P < 0.05). The relation between the leptin expression level in PCa and the BMI was not remarkable (P = 0.447)., Conclusion: Our results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa., ((c) 2008, Asian Journal of Andrology, SIMM and SJTU. All rights reserved.)

Aim: To investigate whether estrogen was involved in relaxation of rabbit cavernous smooth muscle., Methods: Relaxation response of the rabbit cavernous smooth muscles to 17beta-estradiol (0.3, 3, 30 and 300 nmol/L) were observed in vitro. The response of the muscle strips to estrogen after incubation with either actinomycin D (10 micromol/L) or L-NAME (10 micromol/L) were also evaluated. Inside-out mode of patch clamp in a single smooth muscle cell was applied to investigate the Maxi-K channel activities., Results: Estrogen caused a dose-dependent relaxation of the strips precontracted with norepinephrine. The maximal response was noted about 10 minutes after treatment. The estrogen-induced relaxation was prevented by neither actinomycin D nor L-NAME, suggesting that the response was not mediated by gene transcription or nitric oxide (NO). Application of 17beta-estradiol increased the Maxi-K channel activities., Conclusion: 17beta-estradiol may be involved in relaxation of rabbit cavernous smooth muscles via a non-genomic and NO independent mechanism. 17beta-estradiol stimulates Maxi-K channel of the rabbit cavernous myocyte.