Prostate Testosterone Research Articles

Fucoidan Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia (BPH) in Rats.

Benign prostatic hyperplasia (BPH) is a major urological health issue for men globally. Fucoidan, a sulfated polysaccharide, displays diverse bioactivities such as anti-inflammatory, anti-tumor, antioxidant, and immunoregulatory effects. This 28-day study examined the effects of Undaria pinnatifida fucoidan on testosterone-induced BPH in rats. Forty-eight Sprague Dawley (SD) rats were randomly divided into six groups; G1- vehicle control, G2- testosterone alone BPH control group (3 mg/kg), G3- finasteride (10 mg/kg) + testosterone, G4- fucoidan (40 mg/kg) + testosterone, G5- fucoidan (400 mg/kg) + testosterone, and G6- fucoidan alone (400 mg/kg). The animals were observed for clinical signs, body weight, feed consumption, prostate weight, prostate index, and biochemical markers such as tumor necrosis factor-alpha (TNF-α), interleukin- 1β (IL-1β), prostate-specific antigen (PSA) and messenger ribonucleic acid (mRNA) expression of BCL-2-associated X protein (BAX) and B-cell lymphoma-2 (BCL-2) in serum. Testosterone and dihydrotestosterone (DHT) levels were evaluated in both serum and prostate. Fucoidan significantly prevented an increase in prostate weight and prostate index induced by testosterone. DHT levels in the prostate of the intervention groups were significantly lower than in the BPH control group (p <0.05); however, no significant difference was observed in serum levels. Similarly, a significant reduction was observed in serum and prostate testosterone levels in the intervention groups compared to the BPH control group (p <0.05). Biochemical analyses showed PSA levels were significantly lower in the fucoidan groups compared to the BPH control group (p<0.05). Although not statistically significant, fucoidan groups showed a trend of reducing IL-1β and TNF-α levels. Fucoidan demonstrated pro-apoptotic potential in its ability to decrease BCL-2 and increase BAX. Histopathological evidence revealed fewer microscopic lesions in the fucoidan groups compared to the BPH control group. The results suggest Undaria pinnatifida fucoidan can reduce testosterone-induced BPH symptoms in SD rats.

Pharmacological Effects of the Lipidosterolic Extract from Kigelia africana Fruits in Experimental Benign Prostatic Hyperplasia Induced by Testosterone in Sprague Dawley Rats.

The use of phytotherapics is very frequent in men with prostatic diseases, sexual disorders and infertility, and many associations are commercially available. Various vegetable products used as drugs or nutraceuticals are attributed to possess the capacity to exert benefic effects on the reproductive system, and most of these drugs have a rich and varied lipidosterolic fraction, primarily responsible for the effects related to the male genital sphere. Kigelia africana (Lam.) Benth. (Bignoniaceae) is a plant used in African folk medicine as a vegetal remedy for various diseases, including some disorders of the male reproductive system; however, its potential activities have not yet been fully explored. The aim of the present study was to investigate whether the lipidosterolic hexane extract (LHE) from K. africana fruits, analyzed by comprehensive two-dimensional gas chromatography-mass spectrometry/flame ionization detection (GC×GC-MS/FID), can prevent or reverse benign prostatic hyperplasia (BPH) in rats. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for four weeks. β-sitosterol (β-s) was used as positive control. On day 28, the animals were sacrificed by cervical dislocation after anesthesia. Prostates were excised, weighed, and used for macroscopic and histological studies. Testosterone and dihydrotestosterone (DHT) levels in prostate were measured. The results showed that LHE significantly reduced the prostatic weight, prostatic index, prostatic levels of testosterone and DHT, and the histopathological alterations (including the epithelial thickness, stromal proliferation, and lumen area) induced by testosterone. These effects were superior to those demonstrated by β-s and appear to be due to a partial antiandrogenic activity of LHE. The results obtained showed that the LHE can prevent, and reverse testosterone induced prostatic hyperplasia, and support the traditional use of Kigelia africana in some disorders of the reproductive system.

P-Glycoprotein and Androgen Receptor Expression Reveals Independence of Canine Prostate Cancer from Androgen Hormone Stimulation.

Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.

Advanced glycation end products, galectin-3, matrix metalloproteinase-9 activity in men with heart failure and concomitant benign prostatic hyperplasia with androgen deficiency

The aim was to evaluate serum levels of matrix metalloproteinases-9 activity, advanced glycation end products, galectin-3, C-reactive protein in men with heart failure and benign prostatic hyperplasiawith testosterone deficiency. The testosterone level was determined by immune-enzyme analysis. The content of advanced glycation end products in plasma were analysed by quantitative autofluorescence. The metalloproteinases-9 activity was estimated with fluorometry. The level of galectin-3, C-reactive protein was determined by immune-enzyme analysis. 1st group was made up by the men with heart failure and benign prostatic hyperplasia with testosterone deficiency; 2nd group – by the men without testosterone deficiency. The men with heart failure and benign prostatic hyperplasia with testosterone deficiency had a significantly higher level of advanced glycation end products, galectin-3, matrix metalloproteinases-9 activity in comparison with men with heart failure without testosterone deficiency (p&lt;0.001). Correlation relations between serum advanced glycation end products in patients of the main group with age, ejection fraction, testosterone level were determined – r=0.48 (p&lt;0.001), r=-0.62 (p&lt;0.001), r= -0.66 (p&lt;0.001) respectively. Receiver operating characteristic analysis for predictive role in heart failure with preserved ejection fraction have shown high degree of sensitivity and specificity for advanced glycation end products in serum (p&lt;0.001). Middle-aged men with heart failure with preserved ejection fraction and benign prostatic hyperplasia with testosterone deficiency are characterised by increased serum advanced glycation end products, galectin-3, matrix metalloproteinases-9 activity, C-reactive protein. Serum advanced glycation end products are potential biomarkers of development of heart failure with phenotype of preserved ejection fraction in this cohort.

Опыт лечения пациентов с доброкачественной гиперплазией предстательной железы и дефицитом тестостерона в амбулаторной практике

Опыт лечения пациентов с доброкачественной гиперплазией предстательной железы и дефицитом тестостерона в амбулаторной практике

Lower urinary tract symptoms against the background of benign prostatic hyperplasia (LUTS/BPH) and testosterone deficiencyare there any links? General questions of terminology, methodology and age epidemiology

Lower urinary tract symptoms against the background of benign prostatic hyperplasia (LUTS/BPH) and testosterone deficiencyare there any links? General questions of terminology, methodology and age epidemiology

MP45-01 ANDROGENIC TO ESTROGENIC SWITCH IN THE PROSTATE GLAND OF OVERWEIGHT PATIENT

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2018MP45-01 ANDROGENIC TO ESTROGENIC SWITCH IN THE PROSTATE GLAND OF OVERWEIGHT PATIENT Zongwei Wang, Libing Hu, Shulin Wu, Shahin Tabetabaei, Chin-Lee Wu, and Aria Olumi Zongwei WangZongwei Wang More articles by this author , Libing HuLibing Hu More articles by this author , Shulin WuShulin Wu More articles by this author , Shahin TabetabaeiShahin Tabetabaei More articles by this author , Chin-Lee WuChin-Lee Wu More articles by this author , and Aria OlumiAria Olumi More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1440AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The steroid 5-α reductase type 2 (SRD5A2) is critical for prostatic development and growth. Strategies to block SRD5A2 using 5-α reductase inhibitors (5ARI) remain a mainstay in the treatment of benign prostatic hyperplasia (BPH). However, one-third of men are resistant to 5ARI therapies. We previously showed that body mass index (BMI) correlates with increased SRD5A2 gene promoter methylation and decreased protein expression in men with symptomatic BPH. We have demonstrated that there is an androgenic to estrogenic switch when SRD5A2 is absent in the prostate gland. Here we wished to identify whether BMI is associated with the androgenic to estrogenic switch in human prostate tissue. METHODS Prostate specimens were collected from 35 patients who underwent transurethral resection of the prostate for symptomatic BPH at Massachusetts General Hospital. Medical records were reviewed to retrospectively collect clinical and pathological data. Patients were categorized by BMI as lean (less than 25 kg/m2), and overweight (25 kg/m2 or greater). Use and duration of α-blockers and/or 5ARIs was assessed. Methylation of SRD5A2 promoter was assessed using Methylated CpG Island Recovery Assay (MIRA). Prostatic levels of testosterone, dihydrotestosterone and estradiol were measured by HPLC-MS. RESULTS We found that BMI was significantly correlated with methylation of SRD5A2 gene promoter (p<0.05) and absence of SRD5A2 protein expression. Higher BMI was associated with higher prostatic estradiol levels (p<0.05). IIEF-5 score, International Index of Erectile Function Questionnaire score, was negatively associated with BMI (p<0.05). Treatment with 5ARIs dramatically increased the level of prostate testosterone levels and testosterone/estradiol ratio in the prostate specimens (p<0.01, p=0.01, respectively), and decreased the level of dihydrotestosterone (p<0.05). CONCLUSIONS Our study demonstrates for the first time that there is an androgenic to estrogenic switch in the prostate glands of overweight patients. Associated with body weight, somatic epigenetic silencing of SRD5A2 changes the prostatic hormonal milieu, and may modulate prostatic homeostasis and growth. Targeting the estrogenic signaling may serve as an effective treatment strategy in subset of overweight BPH patients. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e597 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Zongwei Wang More articles by this author Libing Hu More articles by this author Shulin Wu More articles by this author Shahin Tabetabaei More articles by this author Chin-Lee Wu More articles by this author Aria Olumi More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Cynanchum wilfordii Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase and Androgen Receptor Activities in a Rat Model.

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats.

Potential of telmisartan in the treatment of benign prostatic hyperplasia.

Benign prostatic hyperplasia (BPH) is a common health problem in ageing men. This study was carried out to investigate the protective effect of telmisartan on testosterone-induced BPH in rats. Fifty-four male Wistar rats (200-250 g) were randomly divided into nine groups (n = 6) and orally treated for 28 consecutive days: group 1 - vehicle normal, olive oil (10 mL/kg); group 2 - BPH model control (10 mL/kg); groups 3-5 - telmisartan (5, 10 or 20 mg/kg, respectively); group 6 - pioglitazone (20 mg/kg); group 7 - celecoxib (20 mg/kg); group 8 - combination of telmisartan (5 mg/kg) and pioglitazone (20 mg/kg); group 9 - combination of telmisartan (5 mg/kg) and celecoxib (20 mg/kg). Animals in groups 2-9 were given testosterone propionate in olive oil (3 mg/kg) subcutaneously 15 min after pretreatments. On day 29, blood was collected for the estimation of serum testosterone and prostate-specific antigen (PSA). The prostates were excised, weighed and subjected to biochemical and histological studies. Testosterone injection induced significant increase in prostatic index, serum testosterone and PSA suggesting BPH as well as increased prostate oxidative stress which were ameliorated with the pretreatment of rats with telmisartan or co-administration of celecoxib and pioglitazone. Histological examination showed that testosterone disrupted the morphology of the prostate epithelial cells evidenced in the involution of the epithelial lining of the acini into the lumen indicating BPH which was reversed by telmisartan. Findings from this study showed that telmisartan alone or in combination with pioglitazone prevented the development of testosterone-induced prostatic hyperplasia.

Triptolide reduces prostate size and androgen level on testosterone-induced benign prostatic hyperplasia in Sprague Dawley rats

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology, characterized by prostatic enlargement coincident with distinct alterations in tissue histology. In the present study, we investigated whether triptolide can prevent testosterone-induced prostatic hyperplasia in rats. Castration was performed via the scrotal route after urethane aesthesia. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP) for two weeks. Triptolide was administered daily by oral gavage at a dose of 100 and 50 μg·kg−1 for 2 weeks, along with the TP injections. On day 14, the animals were humanely killed by cervical dislocation after aesthesia. Prostates were excised, weighed, and used for histological studies. Testosterone and dihydrotestosterone (DHT) levels in serum and prostate were measured. The results showed that triptolide significantly reduced the prostate weight, and the testosterone and DHT levels in both the serum and prostate. Histopathological examination also showed that triptolide treatment suppressed TP-induced prostatic hyperplasia. In conclusion, triptolide effectively inhibits the development of BPH induced by testosterone in a rat model.

Prostate cancer and testosterone replacement therapy: what is the risk?

Prostate cancer and testosterone replacement therapy: what is the risk?

PD20-01 TESTOSTERONE AND CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: A PROPENSITY SCORE MATCHED ANALYSIS

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Prostate & Genitalia I1 Apr 2016PD20-01 TESTOSTERONE AND CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME: A PROPENSITY SCORE MATCHED ANALYSIS Jun Ho Lee and Sung Won Lee Jun Ho LeeJun Ho Lee More articles by this author and Sung Won LeeSung Won Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1414AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Recent studies reported that low total testosterone (T) level is related to the presence of lower urinary tract symptom (LUTS). Because low T is related to LUTS which suggest increase in prostatic urethra pressure and because increase in prostatic urethra pressure is possible cause of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), the relationship between T and CP/CPPS would be inferred. Therefore, we evaluated their relationship. METHODS We conducted a propensity-matched study by identifying men with T<3.5ng/mL among a total of 8,336 men in their 40-50s who had participated in a health examination. A control men (T≥3.5ng/mL) matched for age, metabolic syndrome (MetS), and body mass index (BMI) at 5:1 ratio. Finally, 948 cases (T<3.5ng/mL) and 4740 controls (T≥3.5ng/mL) were selected. The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) was administered. Symptoms were regarded as prostatitis-like symptom if respondents reported perineal or ejaculatory pain and had an NIH-CPSI pain score ≥4. The severity was classified as mild pain (pain score:≥4 but <8) and moderate to severe pain (pain score:≥8). International prostate symptom score, transrectal ultrasonography, uroflowmetry, and post-void residual urine volume were used. The chi-square test, t-test and logistic regression analyses were used for statiscal analysis. RESULTS Before propensity score matching, the mean age, number of MetS components, and mean BMI were significantly greater in T<3.5ng/mL group. After propensity score matching, age, BMI, and number of components of MetS did not differ significantly. Compared to T≥3.5ng/mL group, the prostatitis-like symptom was higher in T<3.5ng/mL group (24.0% vs. 27.4%, P=.001). Additionally, the moderate to severe prostatitis-like symptom was higher in T<3.5ng/mL group (6.2% vs. 9.2%, P=.028). The pain domain, total, and QoL of NIH-CPSI was also higher in T<3.5ng/mL group. The ratio of severe LUTS (12.6% vs. 15.1%, P=.044), maximal flow rate≤10mL/sec (3.8% vs. 5.3%, P=.044), postvoid residual urine volum≥100mL (4.0% vs. 5.6%, P=.035), all of which suggest high pressure in prostate urethra, were significantly higher in T<3.5ng/mL group. After adjusting voided volume during uroflowmetry and total prostate volume, T<3.5ng/mL was significantly related to maximal flow rate≤10mL/sec (OR: 1.402, 95% CI: 1.017-1.934, P=.039) and postvoid residual urine volum≥100mL (OR: 1.410, 95% CI:1.031-1.927, P= .031). CONCLUSIONS T<3.5ng/mL was significantly correlated with the prostatitis-like symptoms. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e451 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Jun Ho Lee More articles by this author Sung Won Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Inhibitory effects of TripTripterygium wilfordii multiglycoside on benign prostatic hyperplasia in rats

The present study was designed to evaluate the inhibitory effects of Tripterygium wilfordii multiglycoside (GTW) against testosterone-induced benign prostatic hyperplasia (BPH) in rats. A total of 45 rats were randomly divided into five groups: Group I, vehicle control group (sham-operated and treated with vehicle); Group II, BPH group; Group III, BPH rats treated with finasteride at a dose of 5 mg·kg−1; and Groups IV and V, BPH rats treated with GTW at dose levels of 10 and 20 mg·kg−1, respectively. The drugs were administered orally once a day for 14 days. Prostate weight, prostatic index, and the testosterone and dihydrotestosterone (DHT) levels in serum and prostate, and the serum prostate specific antigen (PSA) levels were measured; prostate tissues were taken for histopathological examination; and serum biochemical analysis was also performed. The BPH rats displayed an increase in prostate weight, prostatic index with increased testosterone and DHT levels in both the serum and prostate, and increased serum PSA levels. GTW treatment at both doses resulted in significant reductions in prostate weight, prostatic index, testosterone and DHT levels in both the serum and prostate, and serum PSA levels, compared with BPH group. Histopathological examination also indicated that GTW treatment at both doses inhibited testosterone-induced prostatic hyperplasia. Serum biochemical analysis showed that the liver and renal functions were normal. In conclusion, GTW inhibited testosterone-induced prostatic hyperplasia in rats, without host toxicity, providing a basis for the development of GTW as a novel therapy for BPH.

Combined administration of testosterone plus an ornithine decarboxylase inhibitor as a selective prostate‐sparing anabolic therapy

Because of its anabolic effects on muscle, testosterone is being explored as a function-promoting anabolic therapy for functional limitations associated with aging; however, concerns about testosterone’s adverse effects on prostate have inspired efforts to develop strategies that selectively increase muscle mass while sparing the prostate. Testosterone’s promyogenic effects are mediated through upregulation of follistatin. We show here that the administration of recombinant follistatin (rFst) increased muscle mass in mice, but had no effect on prostate mass. Consistent with the results of rFst administration, follistatin transgenic mice with constitutively elevated follistatin levels displayed greater muscle mass than controls, but had similar prostate weights. To elucidate signaling pathways regulated differentially by testosterone and rFst in prostate and muscle, we performed microarray analysis of mRNAs from prostate and levator ani of castrated male mice treated with vehicle, testosterone, or rFst. Testosterone and rFst shared the regulation of many transcripts in levator ani; however, in prostate, 593 transcripts in several growth-promoting pathways were differentially expressed after testosterone treatment, while rFst showed a negligible effect with only 9 transcripts differentially expressed. Among pathways that were differentially responsive to testosterone in prostate, we identified ornithine decarboxylase (Odc1), an enzyme in polyamine biosynthesis, as a testosterone-responsive gene that is unresponsive to rFst. Accordingly, we administered testosterone with and without α-difluoromethylornithine (DFMO), an Odc1 inhibitor, to castrated mice. DFMO selectively blocked testosterone’s effects on prostate, but did not affect testosterone’s anabolic effects on muscle. Co-administration of testosterone and Odc1 inhibitor presents a novel therapeutic strategy for prostate-sparing anabolic therapy.

Differential Effects of Dehydroepiandrosterone and Testosterone in Prostate and Colon Cancer Cell Apoptosis: The Role of Nerve Growth Factor (NGF) Receptors

Tumor growth is fostered by inhibition of cell death, which involves the receptiveness of tumor to growth factors and hormones. We have recently shown that testosterone exerts proapoptotic effects in prostate and colon cancer cells through a membrane-initiated mechanism. In addition, we have recently reported that dehydroepiandrosterone (DHEA) can control cell fate, activating nerve growth factor (NGF) receptors, namely tropomyosin-related kinase (Trk)A and p75 neurotrophin receptor, in primary neurons and in PC12 tumoral cells. NGF was recently involved in cancer cell proliferation and apoptosis. In the present study, we explored the cross talk between androgens (testosterone and DHEA) and NGF in regulating apoptosis of prostate and colon cancer cells. DHEA and NGF strongly blunted serum deprivation-induced apoptosis, whereas testosterone induced apoptosis of both cancer cell lines. The antiapoptotic effect of both DHEA and NGF was completely reversed by testosterone. In line with this, DHEA or NGF up-regulated, whereas testosterone down-regulated, the expression of TrkA receptor. The effects of androgens were abolished in both cell lines in the presence of TrkA inhibitor. DHEA induced the phosphorylation of TrkA and the interaction of p75 neurotrophin receptor with its effectors, Rho protein GDP dissociation inhibitor and receptor interacting serine/threonine-protein kinase 2. Conversely, testosterone was unable to activate both receptors. Testosterone acted as a DHEA and NGF antagonist, by blocking the activation of both receptors by DHEA or NGF. Our findings suggest that androgens may influence hormone-sensitive tumor cells via their cross talk with NGF receptors. The interplay between steroid hormone and neurotrophins signaling in hormone-dependent tumors offers new insights in the pathophysiology of these neoplasias.

Effects of competitive and noncompetitive 5f-reductase inhibitors on serum and intra-prostatic androgens in beagle dogs

Background 5α-Reductase inhibitors (5α-RI) act by inhibiting the conversion of testosterone to dihydrotestosterone (DHT), thereby preventing DHT induced benign prostatic hyperplasia. The existing 5α-RIs can be classified into two types: competitive and noncompetitive. Currently, limited evidence is available concerning the effect differences between the two types of 5α-RI on androgens. The purpose of this study was to assess the effects of competitive and noncompetitive 5α-RIs on serum and intra-prostatic androgens in beagle dogs. Methods Twenty beagles with spontaneous benign prostatic hyperplasia were randomly allocated into two groups: epristeride group (n=10) in which beagles were treated with epristeride at 1 mg/kg once a day for 3 months, and finasteride group (n=10) in which beagles were treated with finasteride at 1 mg/kg once a day for 3 months. The levels of intra-prostatic testosterone and DHT were measured before treatment and on day one after three months medication. Serum levels of testosterone and DHT were measured at the same time points. Changes in androgen levels before and after treatment were analyzed, and comparisons were made within each treatment group and between treatment groups. Results After 3-month treatment, serum and intra-prostatic DHT levels all decreased significantly in both the epristeride and finasteride groups. The change of DHT in serum was significantly higher in the finasteride group (-14% and -43% in epristeride and finasteride groups respectively, with P&lt;0.001); however there was no significant difference in the changes of intra-prostatic DHT between the two groups (-47% and -51% in epristeride and finasteride groups, respectively, P=0.304). The decreases in DHT levels were accompanied by reciprocal increases in serum and intra-prostatic testosterone levels. Changes of testosterone were significantly higher in finasteride group both in serum (20% and 42% in epristeride and finasteride groups, respectively, P&lt;0.001) and in prostate tissue (18% and 29% in epristeride and finasteride groups, respectively, P=0.004). Conclusions Two types of 5T-RI have similar effects in reducing DHT in prostate tissue in beagles. Competitive 5α-RI may reduce serum DHT to a greater scale, and significantly increase testosterone in beagle serum and prostate.

Inhibitory Effects of Isoflavonoids on Rat Prostate Testosterone 5α-Reductase

Testosterone 5α-reductase inhibitors represent important therapeutic drugs for use against androgen-dependent diseases such as benign prostatic hyperplasia, male pattern baldness, and acne. We have searched for inhibitors of rat prostate testosterone 5α-reductase in the cultured broths of many kinds of soil bacteria, and have found that cultured soybean-casein digest broths of certain bacterial strains have a potent inhibitory effect on the enzyme. We tested 10 selected isoflavonoids, including isoflavones and O-methylated isoflavones, for inhibitory effects on rat prostate testosterone 5α-reductase to determine the important structural elements for inhibition of the enzyme. Genistein, biochanin A, equol, and 3′,4′,7-trihydroxyisoflavone showed considerably higher inhibitory effects whereas daidzein, formononetin, glycitein, prunetin, ipriflavone, and 4′,7-dimethoxyisoflavone showed lower inhibitory effects. The IC50 values of genistein, biochanin A, equol, 3′,4′,7-trihydroxyisoflavone, and riboflavin, a positive control, for rat prostate testosterone 5α-reductase were 710 μm, 140 μm, 370 μm, 690 μm, and 17 μm, respectively. Daidzein, genistein, biochanin A, formononetin, and equol are already known to be testosterone 5α-reductase inhibitors, but this is the first characterization of 3′,4′,7-trihydroxyisoflavone as an inhibitor of the enzyme.

Suppressive effects of the antiandrogen agent, chlormadinone acetate and the 5α-reductase inhibitor, dutasteride on prostate weight and intraprostatic androgen levels in rats

The objectives of this study were to investigate whether chlormadinone acetate (CMA, Prostal, CAS 302-22-7) more markedly decreased ventral prostate and seminal vesicle weights and exerted more beneficial effects on intraprostatic androgen levels than dutasteride (DUT, CAS 164656-23-9) in rats. Dose-dependent inhibiting effects on prostate and seminal vesicle enlargement were observed after the 14-day administration of CMA (30, 100 mg/kg/day) and DUT (0.3, 1 mg/kg/day). The prostate atrophy rates calculated as the percentages relative to the vehicle-treated group were 50.5 and 67.9% with 30 and 100 mg/kg CMA and 34.9 and 37.0% with 0.3 and 1 mg/kg DUT, respectively, and the atrophying effect of CMA was significantly greater than that of DUT (p < 0.05). The results of 7-day administration were similar to those of 14-day administration. While CMA dose-dependently and significantly (p < 0.05) reduced the testosterone (T) and dihydrotestosterone (DHT) concentrations in prostate, DUT reduced the DHT concentration but markedly increased the T concentration (20-40 times). Even though it was carried out in rats, this study revealed for the first time that the antiandrogen CMA showed a stronger atrophying effect than the 5alpha-reductase inhibitor DUT on direct comparison. The difference between the atrophying effects of CMA and DUT is considered to be attributed to the present results that CMA reduced the concentrations of both androgens (T and DHT) in prostate but DUT did not, and the fact that CMA has a potent androgen receptor-blocking action but DUT does not.

MP-06.12 Early and Late Levels of Prostate Specific Antigen and Testosterone After Renal Transplant

MP-06.12 Early and Late Levels of Prostate Specific Antigen and Testosterone After Renal Transplant

1971 COMPARATIVE EFFECT OF FINASTERIDE AND DUTASTERIDE ON CROMOGRANIN A LEVELS AS MARKER OF NEUROENDOCRINE DIFFERENTIATION IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

INTRODUCTION AND OBJECTIVES: To verify and to compare in benign prostatic hyperplasia (BPH) patients the effect of finasteride versus dutasteride therapy on chromogranin A (CgA) serum levels, as possible marker of neuroendocrine (NE) differentiation and activity into the prostate gland. METHODS: This is a prospective randomized study in which 60 consecutive men with clinical diagnosis of benign prostatic hyperplasia (BPH) were randomized to a 6-month period of finasteride 5 mg/day versus dutasteride 4 mg/day versus control (no therapy) strategy. Total prostate specific antigen (PSA), testosterone and CgA were analysed in all cases at randomization and therefore at 1, 3 and 6 month interval. RESULTS: In both Group A (finasteride) and Group B (dutasteride), but not in Group C (no therapy) a statistically significant increase (p 0.05) in serum CgA levels was found at 3-months and 6-month interval of therapy when compared with visit 0 .Comparing the three groups,either at 3-month or at 6-month interval, serum CgA was significantly (p 0.05) higher in Group A and Group B than in Group C. At each interval, no significant (p 0.05) difference between Group A and Group B was found. CONCLUSIONS: In our BPH population, 5 alpha reductase inhibitors, with no difference between finasteride and dutasteride, produce a significant increase in serum CgA levels probably related to NE activation into the prostate gland.