Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of pro...Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy （RRP） for clinically-localized prostate cancer. Methods： Serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer （n = 159） and those who were not diagnosed with prostate cancer from biopsy （control group, n = 433）. Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen （PSA）, pathological T stage and pathological Gleason score. Results： Prostate cancer patients and the control group demon- strated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-I and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Oleason score and preoperative PSA. Conclusion： Our data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men. （Asian J Androl 2008 Mar; 10： 207-213）展开更多
We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further inves...We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.展开更多
Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived ...Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived growth factor beta ( PDGFR - β) in aortic vascular smooth muscle tissues (VSMTs). Methods Forty aged male rats were ran- domly divided into 4 groups, group A (placebo group) , group B (2. 5 mg/kg intramuscular injection of TE once a week ) , group C (5.0 mg/kg intramuscular injection of TE once a week ) , group D ( 10. 0 mg/kg intramus- cular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The ex- pression of AR ,ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0. 01 ). Compared with the other groups, average serum TC was also lower in group D (p <0. 05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ±21.74, 125.38 ±28.68 and 101.98 ± 15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg, respectively , the expression of ER - β could be regulated by TE: 92. 34 ± 18. 68, 47. 72 ± 18.12, 82.13 ±23.50, and the expression of PDGFR - β could be regulated as well by TE: 219.70 ±45. 59, 50.16 ±9. 72, 125.36 ±15. 74(Data for AR ,ER-β and PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100 ).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5. 0 mg/kg can stimulate the expression of AR, but inhibite the expres- sion of PDGFR. Testosterone enanthate at the concen- trations of 5. 0 mg/kg and 10. 0 mg/kg can inhibite the expression of ER - β.展开更多
To determine whether the therapeutic effectiveness of testosterone in male elderly coronary heart disease patients is related to the production of nitric oxide (NO), which accounts for the biological activity of endot...To determine whether the therapeutic effectiveness of testosterone in male elderly coronary heart disease patients is related to the production of nitric oxide (NO), which accounts for the biological activity of endothelium derived relaxing factor (EDRF), we studied the regulatory effect of testosterone on production of NO/EDRF in the aorta and cultured vascular endothelial cells. The production of NO/EDRF was detected by the stimulation of cGMP formation in rabbit fetal lung-6 cells. The results showed that testosterone stimulated the production of NO/EDRF in both the aorta and cultured vascular endothelial cells, suggesting that NO/EDRF-dependent vasodilation is one of the mechanism by which testosterone alleviates angina pectoris and improves myocardial ischemia in elderly male coronary heart disease patients.展开更多
AIM:The pathogenesis of hypogonadism in liver cirrhosis is not well understood.Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis.The administ...AIM:The pathogenesis of hypogonadism in liver cirrhosis is not well understood.Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis.The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology,histopathology,cellular proliferation,integrity of testicular barrier and hypophyso- gonadal axis in rats with no ascitic cirrhosis. METHODS:Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride(CCI_4)for 11 wk, were allocated into two groups(n=12,each)to receive recombinant IGF-1(2 μg/100 gd,sc)for two weeks or vehicle.Healthy rats receiving vehicle were used as control group(n=12). RESULTS:Compared to controls,rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However,these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression.In addition,pituitary-gonadal axis was altered,with significant higher levels of FSH(P<0.001 vscontrols)and increased levels of LH in untreated cirrhotic animals.Interestingly,IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH(P=ns vs controls,and P<0.01 vs untreated cirrhotic group). CONCLUSION:The testicular barrier is altered from an early stage of cirrhosis,shown by a reduction of transferrin expression in Sertoli cells,a diminished cellular proliferation and an altered gonadal axis.The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.展开更多
Although testosterone replacement therapy(TRT)is the first-choice method used worldwide for late-onset hypogonadism(LOH),clinical benefits are not seen in all cases.This study was conducted to determine the predictors...Although testosterone replacement therapy(TRT)is the first-choice method used worldwide for late-onset hypogonadism(LOH),clinical benefits are not seen in all cases.This study was conducted to determine the predictors of TRT efficacy for LOH.Fifty-six patients who visited our Men’s Health Clinic(Kawanishi City Medical Center,Kawanishi and Hyogo Medical University,Nishinomiya,Hyogo,Japan)between November 2003 and June 2021 with data available before and after TRT were enrolled.They were divided into responders(Group 1;n=45,accounting for 80.4%)and nonresponders(Group 2;n=11,accounting for 19.6%)based on the clinical response to TRT,including patient satisfaction.Factors noted before TRT included age,body mass index,aging males’symptoms score,sexual health inventory for men,luteinizing hormone,follicular-stimulating hormone,testosterone,free testosterone,prolactin(PRL),estradiol(E2),and testosterone/estradiol(T/E2)ratio in serum.For statistical analysis,a multivariable logistic regression model was used.Univariate analysis revealed PRL(odds ratio TORI:0.9624;95%confidence interval[Cl]:0.9316-0.9943,P<0.05),E2(OR:0.8692;95%Cl:0.7745-0.9754,P<0.05),and T/E2 ratio(OR:1.1312;95%Cl:1.0106-1.2661,P<0.05)to be predictive factors.Multivariate analyses showed that T/E2 ratio was an independent predictive factor(OR:1.1593;95%Cl:1.0438-1.2875,P<0.01).The present results suggest that a low value for T/E2 ratio may predict a reduced response to TRT.The T/E2 ratio threshold to predict nonresponders based on receiver-operating characteristics(ROC)curve analysis was shown to be 17.3.Although additional studies with larger number of patients are necessary,we propose the determination of serum E2 level and testosterone level prior to performing TRT.展开更多
文摘Aim： To investigate the relationships of serum testosterone, insulin-like growth factor （IGF）- 1 and IGF-binding protein （IGFBP）-3 levels with prostate cancer risk and also with known prognostic parameters of prostate cancer in Korean men who received radical retropubic prostatectomy （RRP） for clinically-localized prostate cancer. Methods： Serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 were determined in 592 patients who subsequently received prostate biopsy. Results were compared between patients who eventually received RRP for prostate cancer （n = 159） and those who were not diagnosed with prostate cancer from biopsy （control group, n = 433）. Among the prostate cancer only patients, serum hormonal levels obtained were analyzed in relation to serum prostate specific antigen （PSA）, pathological T stage and pathological Gleason score. Results： Prostate cancer patients and the control group demon- strated no significant differences regarding serum levels of total testosterone, free testosterone, IGF-I and IGFBP-3 across the different age groups. Among the cancer only patients, no significant associations were observed for serum levels of total testosterone, free testosterone, IGF-1 and IGFBP-3 levels with pathological T stage, pathological Oleason score and preoperative PSA. Conclusion： Our data indicate that simple quantifications of serum testosterone and IGF-1 along with IGFBP-3 levels might not provide useful clinical information in the diagnosis of clinically localized prostate cancer in Korean men. Also, our results suggest that serum levels of testosterone, IGF-1 and IGFBP-3 might not be significantly associated with known prognostic factors of clinically localized prostate cancer in Korean men. （Asian J Androl 2008 Mar; 10： 207-213）
基金the National Natural Science Foundation of China(No.30670842)the Natural Science Foundation of Guangdong Province,China(No.5300582).
文摘We have observed earlier that testosterone at physiological concentrations can stimulate tissue factor pathway inhibitor(TFPI)gene expression through the androgen receptor in endothelial cells.This study further investigated the impact of testosterone on TFPI levels in response to inflammatory cytokine tumor necrosis factor-alpha(TNF-α).Cultured human umbilical vein endothelial cells were incubated in the presence or absence of testosterone or TNF-α.TFPI protein and mRNA levels were assessed by enzyme-linked immunosorbent assay and quantitative real-time reverse transcription polymerase chain reaction.To study the cellular mechanism of testosterone’s action,nuclear factor-kappa B(NF-κB)translocation was confirmed by electrophoretic mobility shift assays.We found that after NF-κB was activated by TNF-α,TFPI protein levels declined significantly by 37.3%compared with controls(P<0.001),and the mRNA levels of TFPI also decreased greatly(P<0.001).A concentration of 30 nmol L-1 testosterone increased the secretion of TFPI compared with the TNF-α-treated group.NF-κB DNA-binding activity was significantly suppressed by testosterone(P<0.05).This suggests that physiological testosterone concentrations may exert their antithrombotic effects on TFPI expression during inflammation by downregulating NF-κB activity.
文摘Objectives To investigate the effects of testosterone enanthate (TE) on serum lip- ids and lipoproteins metabolism and the expression of androgen receptor (AR) , estrogen receptor beta ( ER - β) and platelet derived growth factor beta ( PDGFR - β) in aortic vascular smooth muscle tissues (VSMTs). Methods Forty aged male rats were ran- domly divided into 4 groups, group A (placebo group) , group B (2. 5 mg/kg intramuscular injection of TE once a week ) , group C (5.0 mg/kg intramuscular injection of TE once a week ) , group D ( 10. 0 mg/kg intramus- cular injection of TE once a week). All animals were fed freely during 16 - week treatment periods. The ex- pression of AR ,ER - βand PDGFR - β were studied by Western bolt. Results Average serum LDL - C was lower in group D than that in group A ( p < 0. 01 ). Compared with the other groups, average serum TC was also lower in group D (p <0. 05). AR expression in aortic vascular smooth muscle tissues could be regulated by TE: 99.50 ±21.74, 125.38 ±28.68 and 101.98 ± 15.42 for TE concentrations at 2.5 mg/kg, 5.0 mg/kg and 10.0 mg/kg, respectively , the expression of ER - β could be regulated by TE: 92. 34 ± 18. 68, 47. 72 ± 18.12, 82.13 ±23.50, and the expression of PDGFR - β could be regulated as well by TE: 219.70 ±45. 59, 50.16 ±9. 72, 125.36 ±15. 74(Data for AR ,ER-β and PDGFR - β protein band intensity were expressed with x ± s, with control group taken as 100 ).Conclusions This study indicates that androgens have significant effects on serum lipids and lipoprotein metabolism. Testosterone enanthate at 5. 0 mg/kg can stimulate the expression of AR, but inhibite the expres- sion of PDGFR. Testosterone enanthate at the concen- trations of 5. 0 mg/kg and 10. 0 mg/kg can inhibite the expression of ER - β.
文摘To determine whether the therapeutic effectiveness of testosterone in male elderly coronary heart disease patients is related to the production of nitric oxide (NO), which accounts for the biological activity of endothelium derived relaxing factor (EDRF), we studied the regulatory effect of testosterone on production of NO/EDRF in the aorta and cultured vascular endothelial cells. The production of NO/EDRF was detected by the stimulation of cGMP formation in rabbit fetal lung-6 cells. The results showed that testosterone stimulated the production of NO/EDRF in both the aorta and cultured vascular endothelial cells, suggesting that NO/EDRF-dependent vasodilation is one of the mechanism by which testosterone alleviates angina pectoris and improves myocardial ischemia in elderly male coronary heart disease patients.
基金Supported by the Spanish Program I+D,SAF 99/0072 and SAF2001/1672
文摘AIM:The pathogenesis of hypogonadism in liver cirrhosis is not well understood.Previous results from our laboratory showed that IGF-1 deficiency might play a pathogenetic role in hypogonadism of cirrhosis.The administration of IGF-1 for a short period of time reverted the testicular atrophy associated with advanced experimental cirrhosis. The aim of this study was to establish the historical progression of the described alterations in the testes, explore testicular morphology,histopathology,cellular proliferation,integrity of testicular barrier and hypophyso- gonadal axis in rats with no ascitic cirrhosis. METHODS:Male Wistar rats with histologically-proven cirrhosis induced with carbon tetrachloride(CCI_4)for 11 wk, were allocated into two groups(n=12,each)to receive recombinant IGF-1(2 μg/100 gd,sc)for two weeks or vehicle.Healthy rats receiving vehicle were used as control group(n=12). RESULTS:Compared to controls,rats with compensated cirrhosis showed a normal testicular size and weight and very few histopathological testicular abnormalities. However,these animals showed a significant diminution of cellular proliferation and a reduction of testicular transferrin expression.In addition,pituitary-gonadal axis was altered,with significant higher levels of FSH(P<0.001 vscontrols)and increased levels of LH in untreated cirrhotic animals.Interestingly,IGF-1 treatment normalized testicular transferrin expression and cellular proliferation and reduced serum levels of LH(P=ns vs controls,and P<0.01 vs untreated cirrhotic group). CONCLUSION:The testicular barrier is altered from an early stage of cirrhosis,shown by a reduction of transferrin expression in Sertoli cells,a diminished cellular proliferation and an altered gonadal axis.The treatment with IGF-1 could be also useful in this initial stage of testicular disorder associated with compensated cirrhosis.
文摘Although testosterone replacement therapy(TRT)is the first-choice method used worldwide for late-onset hypogonadism(LOH),clinical benefits are not seen in all cases.This study was conducted to determine the predictors of TRT efficacy for LOH.Fifty-six patients who visited our Men’s Health Clinic(Kawanishi City Medical Center,Kawanishi and Hyogo Medical University,Nishinomiya,Hyogo,Japan)between November 2003 and June 2021 with data available before and after TRT were enrolled.They were divided into responders(Group 1;n=45,accounting for 80.4%)and nonresponders(Group 2;n=11,accounting for 19.6%)based on the clinical response to TRT,including patient satisfaction.Factors noted before TRT included age,body mass index,aging males’symptoms score,sexual health inventory for men,luteinizing hormone,follicular-stimulating hormone,testosterone,free testosterone,prolactin(PRL),estradiol(E2),and testosterone/estradiol(T/E2)ratio in serum.For statistical analysis,a multivariable logistic regression model was used.Univariate analysis revealed PRL(odds ratio TORI:0.9624;95%confidence interval[Cl]:0.9316-0.9943,P<0.05),E2(OR:0.8692;95%Cl:0.7745-0.9754,P<0.05),and T/E2 ratio(OR:1.1312;95%Cl:1.0106-1.2661,P<0.05)to be predictive factors.Multivariate analyses showed that T/E2 ratio was an independent predictive factor(OR:1.1593;95%Cl:1.0438-1.2875,P<0.01).The present results suggest that a low value for T/E2 ratio may predict a reduced response to TRT.The T/E2 ratio threshold to predict nonresponders based on receiver-operating characteristics(ROC)curve analysis was shown to be 17.3.Although additional studies with larger number of patients are necessary,we propose the determination of serum E2 level and testosterone level prior to performing TRT.
