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PubMed2002

Dihydrotestosterone and the concept of 5alpha-reductase inhibition in human benign prostatic hyperplasia.

The development of human benign prostatic hyperplasia (BPH) clearly requires a combination of testicular androgens and the ageing process. Although the role of androgens as the causative factor for human benign prostatic hyperplasia is debated, they undoubtedly play, at least, a permissive role. The principal prostatic androgen is dihydrotestosterone. Although not elevated in human benign prostatic hyperplasia, dihydrotestosterone levels in the prostate remain at a normal level with ageing, despite a decrease in the plasma testosterone. Dihydrotestosterone (DHT) is generated by a reduction in testosterone. Two isoenzymes of 5alpha-reductase have been discovered. Type 1 is present in most tissues in the body where 5alpha-reductase is expressed, and is the dominant form in sebaceous glands. Type 2 5alpha-reductase is the dominant isoenzyme in genital tissues, including the prostate. Finasteride is a 5alpha-reductase inhibitor that has been used to treat BPH and male-pattern baldness. At doses used clinically, its major effect is to suppress type 2 5alpha-reductase, because it has a much lower affinity for the type 1 isoenzyme. Finasteride suppresses DHT by about 70% in serum and by as much as 85%-90% in the prostate. The remaining DHT in the prostate is likely to be the result of type 1 5alpha-reductase. The suppression of both 5alpha-reductase isoenzymes with GI198745 results in greater and more consistent containment of serum dihydrotestosterone than that observed with a selective inhibitor of type 2 5alpha-reductase. Physiological and clinical studies comparing dual 5alpha-reductase inhibitors, such as GI198745, with selective type 2, such as finasteride, will be needed to determine the clinical relevance of type 1 5alpha-reductase within the prostate. There have been two large, international multicentre, phase III trials published documenting the safety and efficacy of finasteride in treating human benign prostatic hyperplasia. Combining these two studies, randomised, controlled data are available for 12 months. Non-controlled extension of these data from a subset of patients, who elected to continue on the drug for 3, 4 and 5 years, are also available. Long-term medical therapy with finasteride can reduce clinically significant endpoints, such as acute urinary retention or surgery. According to the meta-analysis of six randomised, clinical trials with finasteride, finasteride is most effective in men with large prostates. A more effective dual inhibitor of type 1 and 2 human 5alpha-reductase may lower circulating dihydrotestosterone to a greater extent than finasteride and show advantages in treating human benign prostatic hyperplasia and other disease states that depend on dihydrotestosterone. A clinical evaluation of potent dual 5alpha-reductase inhibitors may help to define the relative roles of human type 1 and 2 5alpha-reductase in the pathophysiology of benign prostatic hyperplasia and other androgen-dependent diseases.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2006

Systematic review and meta-analysis of Transurethral Needle Ablation in symptomatic Benign Prostatic Hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) constitutes a major clinical problem. Minimally invasive therapies for the treatment of symptomatic BPH include Transurethral Needle Ablation (TUNA), but it is unclear what impact this technique has on the disease and its role among other currently available therapeutic options. The objective of this study is to ascertain the efficacy and safety of TUNA in the treatment of BPH. METHODS: Systematic review of the literature until January 2005 and meta-analysis of clinical studies assessing TUNA in symptomatic BPH. Studies were critically appraised. Estimates of effect were calculated according to the random-effects model. RESULTS: 35 studies (9 comparative, 26 non-comparative) were included. Although evidence was limited by methodological issues, the analysis of relevant outcomes indicates that while TUNA significantly improves BPH parameters with respect to baseline, it does not reach the same level of efficacy as TURP in respect to all subjective and objective variables. Further, its efficacy declines in the long-term with a rate of secondary-treatment significantly higher than of TURP [OR: 7.44 (2.47, 22.43)]. Conversely, TUNA seems to be a relatively safe technique and shows a lower rate of complications than TURP [OR:0.14 (0.05, 0.14)] with differences being particularly noteworthy in terms of postoperative bleeding and sexual disorders. Likewise, TUNA has fewer anesthetic requirements and generates a shorter hospital stay than TURP [WMD: -1.9 days (-2.75, -1.05)]. Scarce data and lack of replication of comparisons hinder the assessment of TUNA vs. other local therapies. No comparisons with medical treatment were found. CONCLUSION: The body of evidence on which TUNA has been introduced into clinical practice is of only moderate-low quality. Available evidence suggest that TUNA is a relatively effective and safe technique that may eventually prove to have a role in selected patients with symptomatic BPH. TUNA significantly improves BPH parameters with respect to baseline values, but it does not reach the same level of efficacy and long-lasting success as TURP. On the other hand, TUNA seems to be superior to TURP in terms of associated morbidity, anesthetic requirements and length of hospital stay. With respect to the role of TUNA vis-à-vis other minimally invasive therapies, the results of this review indicate that there are insufficient data to define this with any degree of accuracy. Overall cost-effectiveness and the role of TUNA versus medical treatment need further evaluation.

Humans↗
PubMed2004

Abnormalities of apoptotic and cell cycle regulatory proteins in distinct histopathologic components of benign prostatic hyperplasia.

INTRODUCTION: Benign prostatic hyperplasia (BPH) is a slowly progressive abnormal glandular enlargement with heterogeneous morphology. Disruption of apoptotic pathways has been suggested as an important regulatory mechanism in this common and significantly morbid disease. METHODS: Prostatic tissue from 20 patients with BPH and no prior or subsequent prostatic carcinoma was obtained by transurethral prostatectomy (TURP) at the University of California Davis. Apoptotic regulatory proteins: BCL2, BAX and p27 were analyzed by immunohistochemistry and evaluated for expression in four distinct histologic patterns: hyperplastic epithelium, nodules, dilated glands and atrophic/inflammatory glands. RESULTS: Particularly striking was the decreased expression of BAX and an abnormal BCL2 : BAX ratio within all nodules relative to expression in other epithelial patterns. p27 expression was decreased in 35% of the hyperplastic epithelial areas and 10% of the nodules. DISCUSSION: Overall, abnormal expression of BCL2, BAX and/or p27 was identified in the hyperplastic epithelium of 19 (90%) of specimens and all 12 (100%) of the hyperplastic nodules. The high frequency of abnormalities in apoptosis regulatory genes, suggests that alteration of apoptotic pathways is important for the development of this condition.

Aged↗
PubMed1992

The clinical assessment of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common pathologic condition to afflict the aging male and the second most common cause of surgical intervention in men older than 60 years of age. Unfortunately, many men currently undergo prostatectomy without rigorous evaluation of their condition in terms of either transition zone hyperplasia or the extent to which this is causing bladder outflow obstruction. METHODS: In this review, the importance of symptoms and symptom scoring systems associated with bladder outflow obstruction due to BPH were considered as well as the use of prostate specific antigen (PBS), uroflowometry, and abdominal and transrectal ultrasound studies in addition to magnetic resonance imaging (MRI). CONCLUSION: Patients undergoing surgical or non-surgical treatment for BPH should be studied by means of a formal symptom score, as well as repeated uroflowometry and abdominal ultrasound. PSA determination should also be made and those patients with values above 4 mg/ml should undergo transrectal ultrasound study and biopsy. Patients with values greater than 10 mg/ml should be considered for systematic biopsy whatever this reveals. MRI, with or without the new endorectal coil, is a promising tool for evaluation of the prostate, but more in a research than routine clinical context.

Antigens, Neoplasm↗
PubMed1995

[A study on international prostate symptom score in the assessment of therapeutic effects and severity of symptoms due to benign prostatic hyperplasia].

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease among elderly men in Japan. Recently, various non-invasive treatment modalities have been developed, however the criteria for the diagnosis and therapeutic effects of BPH have not been established yet. World Health Organization sponsored International Prostate Symptom Score (I-PSS) was devised. The criteria, however, were limited to evaluate the frequency of the subjective symptoms of BPH. In addition, this criteria did not include the quality of life (QOL) score. PATIENTS AND METHODS: We examined I-PSS and a new by modified symptom score for patients who underwent TUR-P. RESULTS: The efficacy of TUR-P could be confirmed by I-PSS, however the criteria proposed in I-PSS and in our modified symptom score were shown to be inadequate to evaluate QOL, and to be not specific scale for BPH. It was demonstrated that objective findings such as peak flow rate, residual urine volume and prostate volume did not correlate with the QOL score, however each objective and subjective significantly improved after TUR-P. CONCLUSION: These results suggested that further effort should be made to establish reliable criteria for the diagnosis and evaluation of therapeutic efficacy considering QOL in BPH patients.

Aged↗
PubMed1995

[The value of self-assessment in management of patients with benign prostatic hyperplasia].

Since benign prostatic hyperplasia (BPH) is a very common and slowly progressive disease which requires surgical treatment in only one-third of those affected, surveillance of the condition on the basis of subjective symptoms is of considerable importance. For this reason, the WHO developed a prostate symptom score (WHO-PSS or I-PSS), which includes both irritative and obstructive symptoms, and which has become accepted all over the world. This score can be used both in investigative studies as a means of monitoring the efficacy of therapy, and as a very good instrument for patient management in the doctor's office.

Aged↗
PubMedDate not supplied

[A trial of using EHF therapy in patients with benign prostatic hyperplasia and its combination with chronic prostatitis].

16 males with benign prostatic hyperplasia (BPH) stage I-II received extremely high-frequency (EHF) therapy alone (group 1), 47 BPH males stage I-II and chronic nonspecific prostatitis EHF therapy plus antibacterial drugs (group 2). Group 3 was control. Clinical pretreatment parameters in group 1 averaged: IPSS--16.6; QOL--4.1; Qmax--7.2 ml/s, RU-135 ml. Three to six months of treatment brought the improvement: IPSS--14.7; QOL--3.2. Qmax rose to 8.3 ml/s, residual urine decreased to 126 ml in 11 (68.7%) patients. The effectiveness of the 2 group treatment was higher: initial IPSS--18.3, QOL-4.5, Qmax--9.2 ml/s, RU--62 ml changed for IPSS--14.1, QOL--3.1 in 43(91.5%) patients, obstruction diminished in 31 (65.9%) patients (Qmax--10.2 ml/s, RU--53 ml). EHF therapy proved effective and safe in BPH alone and especially in BPH combination with chronic nonspecific prostatis.

Aged↗
PubMed2006

[Old and new interventional therapies in the treatment of symptomatic benign prostate hyperplasia (BPH)].

Benign Prostatic Hyperplasia is a common entity among the aging male population. Its prevalence is increasing with age and is around 80% in the over 80-years old. The androgen-estrogen ratio changes in favor of the estrogens, which leads to a growth of prostatic tissue, presenting histologically as hyperplasia. BPH can cause irritative or obstructive symptoms or both. Nowadays we speak of bladder storage or bladder voiding symptoms, summarised as LUTS (Lower Urinary Tract Symptoms). LUTS has a structural and a functional component, the structural being caused by the size of the adenoma itself the functional depending on the muscle tone of the bladder neck and the prostatic urethra. To investigate LUTS, we use validated symptom scores, sonography for residual urine and eventually a urodynamic evaluation. There are 3 grades of BPH. The indication for an interventional therapy is relative in BPH II, and absolute in BPH III. Prior to treatment, other diseases mimicking the same symptoms, have to be ruled out and adequatly treated. Electro-resection of the prostate (TUR-P) remains the standard therapy and the benchmark any new technology has to compete with. TUR-P has good short- and longterm results, but can be associated with a considerable perioperative morbidity, and the learning curve for the operator is long. The most promising of the newer techniques is the Holmium-Laser-Enucleation of the prostate (Laser-TUR-P), showing at least identical short- and median-term results, but a lower perioperative morbidity than TUR-P For several minimally-invasive techniques, indications are limited. TUMT TUNA, WIT and laser-coagulation all produce a coagulation necrosis of the prostatic tissue by thermic damage with secondary tissue shrinking. Urodynamic results however, are not comparable to TUR-P or Laser-TUR-P, and significantly more secondary interventions within 2 to 5 years are required. Minimal-invasive techniques present a favorable alternative for younger patients without complications of BPH, and for older patients with relevant comorbidities, and can usually be performed under local anaesthesia. The morbidity is low and further therapies remain possible later, if necessary.

Catheter Ablation↗
PubMedDate not supplied

The pathophysiology of benign prostatic hyperplasia.

Although benign prostatic hyperplasia (BPH) is one of the most common disease processes affecting the aging male, surprisingly little is known about its pathophysiology. Cause-and-effect relationships have not been established, despite intense research efforts in the last four or five decades aimed at elucidating the underlying etiology of prostatic growth in older men. Previously held notions that the clinical symptoms of BPH (prostatism) are due simply to a mass-related increase in urethral resistance are too simplistic. It is now clear that a significant portion of the symptoms are due to obstruction-induced detrusor dysfunction. Moreover, obstruction may induce a variety of neural alterations in the bladder and prostate that contribute to symptomatology. Undoubtedly, the constellation of cellular pathologies that give rise to the symptoms of BPH will be far more complex than we currently realize. Only by unraveling these complexities, however, will we be able successfully to design alternative strategies to treat, and possibly prevent BPH.

Humans↗
PubMedDate not supplied

Comparison of MR imaging and urodynamic findings in benign prostatic hyperplasia.

OBJECTIVE: In benign prostatic hyperplasia (BPH), it is uncertain whether the size of the prostate is related to the degree of urodynamically demonstrated bladder outlet obstruction. We compared MR imaging findings and urodynamic data in patients with surgically confirmed BPH. MATERIALS AND METHODS: We prospectively studied 43 benign prostatic hyperplasia (BPH) patients in whom transurethral resection of the prostate (TURP) was planned. We obtained T1- and T2-weighted images in the transverse and sagittal planes with a 1.5 Tesla superconducting unit. The predicted volume of the inner gland and the peripheral zone were obtained on T2-weighted transverse images. Prostatic protrusion into the urinary bladder (IB protrusion) and the inner gland ratio (IG ratio: inner gland volume/total prostatic volume) were determined. RESULTS: IB protrusion and inner IG ratio were significantly greater in patients with severe stenosis than in those without. A surgical capsule (SC) was seen in 20 of 25 patients (80%) with severe stenosis and 8 of 18 (44%) of those without it. The accuracy of IB protrusion + IG ratio, IB protrusion + surgical capsule, and IB protrusion + IG ratio + surgical capsule was 89%, and that of IG ratio + surgical capsule was 86%. CONCLUSION: The inner gland ratio, protrusion into the bladder, and presence of surgical capsule were the most important factors in bladder outlet obstruction. The probability of outlet stenosis increases in patients with more than two of these criteria.

Aged↗
PubMed1993

Relationship between epidermal growth factor and its receptor in human benign prostatic hyperplasia.

Human benign prostatic hyperplasia (BPH) samples were analyzed to evaluate the presence of immunoreactive epidermal growth factor (irEGF) and EGF receptor (EGFR). In all BPH samples examined both peptide and its receptor were present. Scatchard analysis of binding data of [125I]EGF showed two classes of binding sites with high and low affinity. Intratissular irEGF concentrations showed a significant inverse linear correlation with EGFR levels. Two groups of samples can be identified: the first showing high irEGF concentrations and low levels of EGF binding sites; the second low irEGF and high concentrations of EGFR. The simultaneous presence of EGF and its receptor in BPH samples indicates that this growth factor may act in an autocrine/paracrine manner in human prostatic tissue. The inverse relationship between EGF and the two sites of EGFR lead one to hypothesize that EGF itself could play a central role in determining receptor cell surface availability.

Aged↗
PubMed1999

[Research and development called for thermotherapy of prostatic hyperplasia].

Symptomatic benign prostatic hyperplasia is to be considered an endemic disease, and the treatment of these problems of elderly men constitutes a substantial drain on health care resources. Transurethral microwave thermotherapy (TUMT) is one of many new treatment methods introduced in Sweden since the beginning of the decade. The article consists in a review of results obtained with TUMT, and discussion of further development of the technique at present under way in this country.

Humans↗
PubMed1999

Elastin gene expression in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly a stromal process, showing an increased ratio of stromal to epithelial elements, a collagen type III downregulation, and a collagen types I and IV upregulation. Little is known about elastin gene expression in BPH tissues due to difficulties related to extensive alternative splicing of the elastin gene. Therefore, we analyzed and quantified elastin gene expression in BPH. METHODS: A competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR) quantitative technique was used, and a quantitative elastin mRNA analysis with normal (n = 10) and BPH (n = 12) tissues was performed with two newly designed elastin primers. Small tissue samples (4-8 mg) were homogenized and sonicated, and cDNA was synthesized from mRNA using a RT reaction. Various target (wild-type) elastin cDNAs with unknown concentrations were competitively coamplified with known serial dilutions of the control mutant template, differing from the target cDNA by a short deletion. Gel fractions and computerized densitometry, were performed and cDNA concentration was calculated by linear regression. RESULTS: The primers identified in our study (BOB-1 and BOB-2) accurately amplified a consistent length of the elastin cDNA, avoiding areas of alternative splicing. The average elastin mRNA concentration in BPH tissues was 53 attomole/mg +/- 11.6 vs. 140.6 attomole/mg +/- 19.6 in normal prostatic tissue (P = 0.019). The variation within every sample was less than 10%. CONCLUSIONS: Our observations suggest a significant downregulation (70%) of the elastin mRNA gene in the transition zone of BPH patients.

Aged↗
PubMed2002

Intakes of energy and macronutrients and the risk of benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is a common disease of older men. Although the etiology remains unclear, nutritional factors may have an effect on the disease. OBJECTIVE: Because the literature on the relations between macronutrient intakes and BPH risk is limited, we examined these relations among men in the Health Professionals Follow-up Study. DESIGN: We followed men aged 40-75 y from baseline in 1986 to 1994. Total BPH cases (n = 3523) comprised men who reported BPH surgery (n = 1589) or who did not undergo surgery but scored 15-35 points on the lower urinary tract symptom questionnaire of the American Urological Association (n = 1934); non-cases were men who scored < or = 7 points (n = 24388). Odds ratios (ORs) and 95% CIs were calculated by using multivariate logistic regression. RESULTS: The ORs rose with increasing total energy intake in a comparison of the highest and lowest quintiles for total BPH (OR: 1.29; 95% CI: 1.14, 1.45) and symptoms of BPH (1.43; 1.23, 1.66). Energy-adjusted total protein intake was positively associated with total BPH (1.18; 1.05, 1.33) and BPH surgery (1.26; 1.06, 1.49). Energy-adjusted total fat intake was not associated with risk of total BPH, but intakes of eicosapentaenoic, docosahexaenoic, and arachidonic acids were associated with a moderate increase in risk of total BPH. CONCLUSIONS: We observed modest direct associations between BPH and intakes of total energy, protein, and specific long-chain polyunsaturated fatty acids. Because eicosapentaenoic, docosahexaenoic, and arachidonic acids are highly unsaturated fatty acids, our findings support a possible role of oxidative stress in the etiology of BPH.

Adult↗
PubMed2002

Calculated fast-growing benign prostatic hyperplasia--a risk factor for developing clinical prostate cancer.

OBJECTIVE: Whether there is an association between the development of benign prostatic hyperplasia (BPH) and clinical prostate cancer is controversial. The present report tests the hypothesis of an association between BPH growth and the development of clinical prostate cancer by examining stage, grade and PSA-level in men with recently discovered clinical prostate cancer with slow or fast-growing BPH. If the hypothesis is true, men with fast-growing BPH would have a more advanced clinical prostate cancer. MATERIAL AND METHODS: Two hundred and twenty patients in whom a clinical prostate cancer was diagnosed were consecutively included. The prevalence of atherosclerotic disease, non-insulin-dependent diabetes mellitus (NIDDM) or treated hypertension was provided by the respective patient's medical history. Tallness, body weight, waist measurement, hip measurement and blood pressure were determined. The body mass index (BMI) and waist/hip ratio (WHR) were calculated. Blood samples were drawn to determine triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol, uric acid, ALAT and the fasting plasma insulin level. The prostate gland volume was measured using transrectal ultrasound. The annual BPH growth rate was calculated, assuming that the total prostate gland volume was 20 mL at the patient age of forty. The prostate cancer diagnosis was established using the technique of transrectal ultrasound-guided automatic needle biopsy of the prostate. RESULTS: Men with clinical prostate cancer, PSA <50 ng/mL, and with fast-growing BPH had a higher systolic (p = 0.009) and diastolic (p = 0.020) blood pressure, were taller (p < 0.001) and more obese, as determined by body weight (p < 0.001), BMI (p = 0.005), waist measurement (p < 0.001) and hip measurement (p = 0.003). They also had a higher fasting plasma insulin level (p = 0.014) and a lower HDL-cholesterol level (p = 0.067) than men with slow-growing BPH. Moreover, men with clinical prostate cancer, PSA <50 ng/mL, and fast-growing BPH had more pronounced clinical prostate cancer, as measured by grade (p = 0.029) and PSA-level (p = 0.016), than men with slow-growing BPH. In the total material, including men with clinical prostate cancer, PSA >/=50 ng/mL, men with fast-growing BPH also had a higher prevalence of NIDDM (p = 0.039) and a borderline statistical significance for higher stage (p = 0.09) than men with slow-growing BPH. The BPH growth rate was significantly associated with the clinical prostate cancer grade (p = 0.018) and PSA-level (p = 0.002) but not with the clinical cancer stage in a multivariate statistical analysis. CONCLUSIONS: This report confirms findings in previous studies that fast-growing BPH is a risk factor for NIDDM, hypertension, tallness, obesity, dyslipidaemia and hyperinsulinaemia. The present report extends this list of risk factors to include atherosclerotic disease manifestations, hyperuricaemia and higher ALAT levels. The study suggests that fast-growing BPH is a risk factor for developing clinical prostate cancer and, thus, supports the hypothesis of an association between the development of BPH and clinical prostate cancer. The study generates the hypothesis that clinical prostate cancer is a component of the metabolic syndrome and that insulin is a promoter of clinical prostate cancer.

Age Distribution↗
PubMed1994

Influence of benign prostatic hyperplasia, testosterone and age on serum levels of prostate specific antigen.

Prostate specific antigen (PSA) and PSA-density (PSAd) were studied in 120 symptomatic patients with benign prostatic hyperplasia at digital rectal examination. PSA and PSAd were measured before and 3 months after transurethral resection. Comparisons were made between patients in whom histologic examination showed benign hyperplasia and those with histologically demonstrated prostatic cancer. The influence of age and of serum testosterone on PSA and PSAd was determined. PSAd in benign prostatic hyperplasia was the same in the transition zone (the adenomas) and the peripheral zone (mean 0.065), indicating no increased synthesis or leakage of PSA. PSAd with cut-off value 0.10 ng x ml-1 x cc-1 showed higher sensitivity and positive predictive value (75% vs 50% and 0.33 vs 0.15, respectively) in nonpalpable prostatic cancer than did PSA with cut-off at 4 ng x ml-1. No statistically significant influence of testosterone and/or age on serum-PSA or PSAd was found.

Age Factors↗
PubMed1997

[Improved discrimination between prostatic carcinoma and benign prostatic hyperplasia by determination of free prostate-specific antigen percentage].

We investigated whether the free-to-total prostate-specific antigen (PSA) ration (f-PSA/t-PSA ratio; i.e. percentage of free PSA) represents a better discriminator for the detection of cancer of the prostate (CaP). In a retrospective analysis, the percentage of free PSA was determined in the sera of 35 patients with histologically proven benign prostatic hyperplasia (BPH) and 35 patients with clinically localized CaP. Patients with urolithiasis (n = 33) served as a control group. Serum levels of free PSA and total PSA were determined employing a chemiluminescent enzyme immunoassay. Patients with CaP demonstrated a lower percentage of free PSA (median: 8.7) than patients with BPH (median: 20.0; P < 0.001). Determination of the percentage of free PSA enhances the differentiation between BPH and CaP and may reduce the number of unnecessary biopsies in patients with an elevated PSA. Confirmation of our preliminary results is required.

Aged↗
PubMed2003

Gene expression analysis of prostate hyperplasia in mice overexpressing the prolactin gene specifically in the prostate.

The probasin (Pb)-PRL transgenic mice that overexpress the rat PRL gene specifically in the prostate develop a dramatic enlargement of the prostate gland. The objective of this study was to characterize the molecular mechanisms involved in the prostate hyperplasia seen in the Pb-PRL transgenic mice. cDNA microarray analysis was used to identify differentially expressed transcripts in the hyperplastic prostates of 6-month-old transgenic mice compared with age-matched controls. We report the identification of 266 genes (175 up-regulated and 91 down-regulated) that were differentially expressed in the enlarged transgenic prostates compared with controls. Subsequential real-time RT-PCR was used to verify a set of differentially regulated transcripts. The hyperplastic prostates of Pb-PRL transgenic mice demonstrate a molecular pattern supporting the importance of reduced degree of apoptosis for the development of the phenotype. Immunohistochemical analysis of apoptotic activity using two different markers of apoptosis (single-stranded DNA and activated caspase-3) were performed, and the results showed diminished apoptosis activity in the prostate of Pb-PRL transgenic mice compared with control prostates. The increased stromal/epithelial ratio of the Pb-PRL transgenic prostate together with up-regulation of a significant fraction of genes involved in tissue remodeling activity, including the synthesis and degradation of the extracellular matrix and changes in protease activity, suggest that activation of the stroma is involved in the development of prostate hyperplasia. Overall, the differentially expressed transcripts identified in this study show many molecular similarities between the prostate hyperplasia of PRL-transgenic mice and human prostate pathology, including both benign prostatic hyperplasia and prostate cancer.

Androgen-Binding Protein↗