Canine Benign Prostatic Hyperplasia Research Articles

Comparative Serum Proteome Profiling of Canine Benign Prostatic Hyperplasia before and after Castration.

BPH is the most prevalent prostatic condition in aging dogs. Nevertheless, clinical diagnosis and management remain inconsistent. This study employed in-solution digestion coupled with nano-liquid chromatography tandem mass spectrometry to assess serum proteome profiling of dogs with BPH and those dogs after castration. Male dogs were divided into two groups; control and BPH groups. In the BPH group, each dog was evaluated at two time points: Day 0 (BF subgroup) and Day 30 after castration (AT subgroup). In the BF subgroup, three proteins were significantly upregulated and associated with dihydrotestosterone: solute carrier family 5 member 5, tyrosine-protein kinase, and FRAT regulator of WNT signaling pathway 1. Additionally, the overexpression of polymeric immunoglobulin receptors in the BF subgroup hints at its potential as a novel protein linked to the BPH development process. Conversely, alpha-1-B glycoprotein (A1BG) displayed significant downregulation in the BF subgroup, suggesting A1BG's potential as a predictive protein for canine BPH. Finasteride was associated with increased proteins in the AT subgroup, including apolipoprotein C-I, apolipoprotein E, apolipoprotein A-II, TAO kinase 1, DnaJ homolog subfamily C member 16, PH domain and leucine-rich repeat protein phosphatase 1, neuregulin 1, and pseudopodium enriched atypical kinase 1. In conclusion, this pilot study highlighted alterations in various serum proteins in canine BPH, reflecting different pathological changes occurring in this condition. These proteins could be a source of potential non-invasive biomarkers for diagnosing this disease.

Establishment of hormone-induced canine benign prostatic hyperplasia model: A prospective, controlled study

PurposeTo evaluate the feasibility of the establishment of a more efficient hormone-induced canine benign prostatic hyperplasia (BPH) model. MethodsThis prospective pilot study included a total of 16 male beagle dogs who underwent dihydrotestosterone and β-estradiol treatment after castration. They were randomly divided into three groups; eight beagles in group A with 1.0 ml hormone treatment, four beagles in group B with 0.8 ml hormone treatment, and four beagles in group C with 1.2 ml hormone treatment, each according to the table of random digit. The size of the prostate was measured using magnetic resonance imaging before and 4, 8, and 12 weeks after intramuscular injection of hormone drugs. Prostate size larger than 18 g was regarded as BPH in dogs. ResultsBeagle dogs in all three groups were successfully modeled for BPH. The experimental group A (n = 8) was successfully modeled after 4 weeks of 1.0 ml hormone treatment, while the control group B (n = 4) was successfully modeled after 8 weeks of 0.8 ml hormone treatment, and the control group C (n = 4) was successfully modeled after 12 weeks of 1.2 ml hormone treatment. ConclusionsAppropriate dose of hormone can significantly shorten the time of successful establishment of canine BPH model, and an increase in hormone dosage can inhibit prostatic hyperplasia.

Prostatic fluid composition and semen quality in dogs with benign prostatic hyperplasia undergoing treatment with osaterone acetate.

Benign prostatic hyperplasia (BPH) may alter prostatic fluid biochemical composition causing reduced fertility. Osaterone acetate (OA) is an androgen receptor antagonist marketed for treatment of canine BPH. Little information exists on effects of OA administration on biochemical composition of canine prostatic fluid and its role on fertility. The aim of this research was to study biochemical composition of prostatic fluid and its role on semen quality in dogs with BPH undergoing treatment with OA. Eight intact, 5-11-year-old dogs with benign prostatic hyperplasia were treated orally with OA at a dose of 0.25-0.5mg/kg once daily for seven days. Prostatic volume, semen evaluation and a biochemical analysis of prostatic fluid were performed on the day before treatment (D0), D60, D120, D180 and D240. A significant reduction (57% and 61%) of prostatic volume was observed at D60 and D120, respectively, and a significant reduction (20%) of normal spermatozoa was observed at D60 coincident with a significant increase of sperm tail defects, which disappeared during the course of the treatment. Prostatic fluid composition did not vary during the OA treatment except for zinc (Zn2+ ) with a significant increase at D120 and D180 correlated with the return to normal sperm values. In conclusion, canine Zn2+ prostatic fluid concentrations decrease during development of BPH and return to normal during treatment with OA. Zn2+ is an important electrolyte for semen quality, suggesting that oral Zn2+ supplementation might be considered a treatment to improve semen quality.

An investigation on the relevance of prolactin, insulin-like growth factor-1 and 25-hydroxyvitamin D3 (25-OHD3 ) in canine benign prostatic hyperplasia in a predisposed breed model.

Serum concentrations of prolactin (PRL), insulin‐like growth factor‐1 (IGF‐1) and 25 hydroxyvitamin D3 (25‐OHD3) were analysed to investigate their possible involvement in the pathogenesis of benign prostatic hyperplasia (BPH). For this, dogs of the Rhodesian Ridgeback (RR) breed were used because of a verified breed disposition for the development of BPH. Labrador Retrievers (LR) served as controls. The prostate gland status was characterised by the prostate gland volume, clinical signs of BPH (haemospermia and sonographic findings) and the plasma concentration of canine prostate‐specific arginine esterase (CPSE). Breed specificity in the RR was expressed by a correlation of PRL with breed (p < 0.05). Similar relationships existed in the dogs with normal CPSE (CPSEn) with respect to the IGF‐1 concentrations (LR: p < 0.05). The latter were negatively correlated with prostatic volume and age (both p < 0.05). Concentrations of 25‐OHD3 were tendentially (p = 0.18) lower in the RR with increased CPSE (CPSEi) compared with the CPSEn LR and RR showing clinical signs of BPH. A negative correlation between serum 25‐OHD3 and age (p < 0.05) existed in the CPSEi RR. Proof of 25‐OHD3 in prostatic secretion proved to be a breed specific feature in the RR (p < 0.0001). For all RR dogs showing clinical signs of BPH, a close to significant (p = 0.06) positive correlation with prostate gland volume was found. The results of the present study reveal no clear hints towards the significance of PRL and IGF‐1 in the pathogenesis of canine BPH. In the RR breed there were indications of a causal relationship with age‐dependent changes in the vitamin D metabolism. The data suggest the possibility of preventing or treating canine BPH by administering vitamin D or substances involved in the intraprostatic vitamin D metabolism.

Overexpression of GDNF and FGF-1 in Canine Benign Prostatic Hyperplasia: Evidence for a Pathogenetic Role of Neural Growth Factor

Benign prostatic hyperplasia (BPH) is common in aged dogs, but the pathogenesis has not been clearly elucidated. A total of 33 male Iranian dogs of mixed breed and in three age groups (under 3 years [n=10]; 3-6 years [n=15]; over 6 years [n=8]), were investigated. BPH was confirmed by ultrasonography and histopathology in 13 cases. The highest prevalence of BPH was in the 3-6 years age group (8/15; 53.3%). Examination of sections of prostate that had been stained with Masson's trichrome revealed that the intensity of stromal smooth muscle cell staining (P<0.05) and the number of fibroblasts (P=0.002) were significantly increased in BPH compared with normal prostate glands. Prostate cells from dogs with BPH (n=13) had a significantly higher intensity of cytoplasmic immunolabelling with antibodies against glial cell line-derived neurotrophic factor (GDNF), cytokeratin (CK) AE1/AE3, vimentin, fibroblast growth factor-1 (FGF-1) and prostate-specific antigen (PSA), compared with normal prostate glands (n=20) (P=0.001), except for PSA, which was negative in both normal and BPH affected prostates. The overexpression of GDNF and FGF-1 in stromal and epithelial cells of prostate glands of dogs with BPH suggests that GDNF has a paracrine or autocrine role in stimulating cellular proliferation. GDNF overexpression may also play a pathogenetic role in promoting chronic prostatitis and increasing fibrosis and the smooth muscle component of the prostate gland in BPH.

Prostatic artery embolization with polyethylene glycol microspheres: evaluation in a canine spontaneous benign prostatic hyperplasia model

BackgroundProstatic artery embolization (PAE) is a minimally invasive technique for the management of symptomatic benign prostatic hyperplasia (BPH) relieving the lower urinary tract symptoms in patients. Various embolic agents have been tested in animal models and subsequently used in human patients. The purpose of this study was to evaluate the technical feasibility, effectiveness, and safety of PAE with polyethylene glycol microspheres in a canine spontaneous BPH model.ResultsFive adult male Beagle dogs (4.78 ± 1.11 years) were diagnosed by tranrectal ultrasonography of spontaneous BPH (prostate volume > 18 ml) and underwent PAE with polyethylene glycol microspheres (400 ± 75 μm). PAE procedures were performed successfully in all dogs. After PAE, all dogs were inspected for potential procedure-related complications during 1 month of follow-up. No major complications were observed any animal. Follow-up angiography was performed in each animal at 1 month of follow-up. Recanalization was demonstrated in all the embolized prostatic arteries or main branches at the end of the study. Magnetic Resonance Imaging (MRI) evaluations were performed immediately before PAE as baseline data, and 1 week, 2 weeks and 1 month after PAE. MRI study showed that the prostate shrank substantially with ischemic necrosis in each dog. There was a significant reduction in the mean prostate volume at 2 weeks and 1 month compared with the baseline data, from 19.95 ± 1.89 mL to 13.14 ± 2.33 and 9.35 ± 2.69 mL (p < 0.001), respectively. Histopathological study was conducted after 1-month follow-up angiography and confirmed the therapeutic responses with diffuse glandular atrophy and interstitial fibrosis.ConclusionsThe findings of the present study support that PAE with the use of polyethylene glycol microspheres is a safe and feasible procedure that may induce a significant shrinkage of prostate due to the local ischemia and secondary glandular atrophy. Early recanalization of target arteries remains to be further addressed in both laboratory investigation and clinical practice.

Quantitative bidimentional and Doppler ultrasound assessment of the effect of a GnRH antagonist on canine prostatic hyperplasia

The objectives of this article were: a) To describe the effect of a single administration of the third generation GnRH antagonist, acyline, on canine benign prostatic hyperplasia (BPH) b)To quantitatively compare parenchyma echogenicity, heterogeneity (SD echogenicity) and blood flow in hyperplastic and treated prostate glands. Seven mixed bred dogs, 11.14 ± 0.8 years of age, weighing 8.5 ± 1.4 (3.8–15.6) kg, with BPH were included in this study and administered acyline 330 mg/kg sc (day 0). Then the dogs were examined by B Mode and Doppler ultrasound on days 15, 30 and 60 after treatment. Parenchymal frozen images were digitally analyzed. On day −7, prostatic volume was 1.60–5.36 fold (volume ratio) enlarged in relation to the expected volume. Prostatic volume decreased up to a mean of −38.44% (P < 0.01; range −32.2 to −70.9%) on day 30 to gradually increase towards pretreatment values. A correlation between volume ratio and nadir treatment volume was also found (r = - 0.87; P < 0.05). Mean parenchyma echogenicity (P < 0.01) and heterogeneity (P < 0.01) diminished in all the post treatment evaluations. Pretreatment intraprostatic cysts disappeared at the time point of peak treatment effect. Prostatic arteries RI increased on day 30, being different from day −7 and also from day 60 values (P < 0.05). It was concluded that a single administration of a third generation GnRH antagonist safely decreased prostatic volume and parenchyma and blood flow abnormities associated with canine BPH during 30 days. Monthly administrations of this treatment could represent a rapid, efficient and safe therapeutic option for BPH.

Changes in the oxidative stress factors and inflammatory proteins following the treatment of BPH-induced dogs with an anti-proliferative agent called tadalafil.

Finding a medical treatment which can combat cell proliferation and relax smooth muscles in canine benign prostatic hyperplasia (BPH) appears to be imperative. This study aimed to evaluate the oxidative stress and inflammatory proteins following the treatment of dogs induced for BPH with an anti-proliferative agent called tadalafil. Twenty-five adult intact male dogs were randomly designated into five groups (n=5): Control group was not induced for BPH and not treated with tadalafil; dogs induced for BPH by testosterone enanthate and estradiol benzoate and treated with tadalafil (5mg/day P.O.); dogs which received tadalafil (5mg/day P.O.); dogs induced for BPH and treated with castration; and dogs induced for BPH. Oxidative stress factors (glutathione peroxidase [GPX], superoxide dismutase [SOD], catalase) and inflammatory proteins (haptoglobin, serum amyloid A [SAA], malondialdehyde [MDA]) were measured in the blood serum for four sequential weeks. Glutathione peroxidase and SOD serum levels declined in dogs in the BPH-induced group compared to those in the control group. Those levels diminished in BPH-induced castrated and tadalafil-treated groups. The changes in the GPX and SOD serum concentrations were not significant between the BPH-induced castrated group and BPH-induced tadalafil-treated group. Moreover, MDA concentration increased slightly in groups with BPH and groups which were castrated. Generally, however, there were no significant differences in the MDA serum concentrations between other groups. Haptoglobin and SAA concentrations increased in BPH-castrated group. Also, the differences in haptoglobin and SAA were not significant between the groups. Tadalafil could not control oxidative stress and inflammatory mediators which happened during BPH in dogs.

Survivin and Sox9: Potential Stem Cell Markers in Canine Normal, Hyperplastic, and Neoplastic Canine Prostate.

Canine prostatic carcinoma is a relevant model for human prostatic carcinoma. Survivin is proposed as a biomarker of malignancy in human prostatic cancer. Sox9 is a stem cell marker required for prostate development and expressed in several adult tissues. The aims of the present study were to evaluate the patterns and expression levels of 2 putative stem cell markers, survivin and Sox9, in canine benign prostatic hyperplasia (BPH) and prostatic carcinoma to investigate their potential as stem cell markers. Immunohistochemistry with specific antibodies was performed on 3 samples of normal prostate gland, 18 samples of canine BPH, and 16 samples of prostatic carcinoma. The basal cell layer of normal and hyperplastic prostatic lobules had nuclear Sox9 immunolabeling and nuclear and rarely cytoplasmic survivin immunostaining, identifying them as potential stem cell markers. Significantly more frequent survivin and Sox9 expression (≥10% of nuclei) was observed in prostatic carcinoma as compared with BPH. The potential coexpression of survivin with Sox9, androgen receptor, and p63 was also investigated in selected BPH and prostatic carcinoma cases with immunofluorescence, and a partial colocalization was observed. Results indicate that Sox9 and survivin could be considered markers of stemness in canine prostate cells. Given its role in proliferation, cells in the basal cell layer with nuclear survivin expression are likely to be transit-amplifying cells that maintain some stem cell proprieties.

Canine prostate models in preclinical studies of minimally invasive interventions: part II, benign prostatic hyperplasia models.

Canine prostate is widely used as animal model in the preclinical evaluation of emerging therapeutic interventions. Spontaneous benign prostatic hyperplasia (BPH) is common in adult intact male dogs with two distinct pathological types: glandular and complex form of prostatic hyperplasia. The complex form of prostatic hyperplasia, usually occurring in older dogs, represents an ideal model because of its unique pathologic feature, including not only glandular hyperplasia but also an increase in prostate stromal components. The limited commercial availability of adult dogs with spontaneous BPH motivates experimentally induced BPH in young dogs. Hormone-induced canine BPH model has been well established with various hormonal treatment regimens and administration approaches. The goal of this review is to provide the veterinary background in spontaneous BPH in dogs, summarize the techniques in hormonal induction of canine BPH, and highlight the pathological and clinical limitations of the canine models that may lead to distinct therapeutic responses compared to clinical trials in humans.

Is STAT3 and PTEN Expression Altered in Canine Prostate Cancer?

Signal transducer and activator of transcription 3 (STAT3) and phosphatase and tensin homologue (PTEN) are, respectively, an oncogene and tumour suppressor gene whose dysregulated expression in human prostate cancer is associated with increased malignancy and poor prognosis. Both markers were evaluated in 12 samples of canine benign prostatic hyperplasia (BPH) and 17 canine prostatic carcinomas (PCs) by immunohistochemistry, to understand their possible role in canine prostate carcinogenesis. STAT3 was expressed in 25% and 82.35% of BPH and PC, respectively, with a significantly higher number of STAT3-positive cells in malignant compared with hyperplastic lesions. Three PCs had occasional nuclear expression of STAT3. PTEN was expressed in BPH and PC with a similar distribution and percentage of positive cells; however, four PCs were PTEN negative. Solid PCs contained more STAT3-positive and fewer PTEN-positive cells compared with the other subtypes. A reduced number of PTEN-positive cells was observed in PCs with a high Gleason score (GS10), while no association was demonstrated between STAT3 expression and Gleason score. The data suggest that overexpression of STAT3 and downregulation of PTEN may be an important step in canine prostate carcinogenesis and both markers may be related to the histological subtypes of PC and the degree of differentiation of neoplastic cells.

Inhibition of spontaneous canine benign prostatic hyperplasia by an Urtica fissa polysaccharide fraction.

In this study, we investigated the inhibition of spontaneous canine benign prostatic hyperplasia by a crude polysaccharide fraction extracted from Urtica fissa roots and stems. After oral administration of U. fissa polysaccharide fraction for 3 months, the dog prostatic volume reduced significantly when compared to that before treatment using CT examination. The high-dosage U. fissa polysaccharide fraction (120 mg/kg body weight/day) and finasteride (0.5 mg/kg body weight/day) treatments showed both almost 30 % reduction of the initial prostatic volume. At the end of the administration of U. fissa polysaccharide fraction, the prostates were excised, and the volumes were measured by water displacement. The prostatic volume showed significant decrease by 11 %, 15 %, and 21 % for the 30, 60, and 120 mg/kg/day U. fissa polysaccharide fraction treatment groups, respectively, compared to the control group. Histological observation found that U. fissa polysaccharide fraction inhibited the dog prostatic epithelial cells proliferation and enlarged glandular lumen diameter. The crude polysaccharide fraction of U. fissa is a possible new candidate for the treatment of benign prostatic hyperplasia.

Immunohistochemical expression of heat shock proteins, p63 and androgen receptor in benign prostatic hyperplasia and prostatic carcinoma in the dog.

This study compared heat shock proteins Hsp60, Hsp72 and Hsp73, along with p63 and androgen receptor (AR) immunoexpression between 16 cases of benign prostatic hyperplasia (BPH) and 11 prostatic carcinomas (PCa) in dogs. The proportion of Hsp60-positive cells was higher in PCa compared with BPH (P = 0.033), whereas the frequency and intensity of Hsp73 immunostaining did not differ significantly between the two groups. Hsp72-immunostained nuclei formed a discontinuous layer along the basement membrane in BPH, whereas cells in this layer in PCa were negative or weakly positive. Hsp72 nuclear score showed significant positive associations with both p63 (P = 0.016) and AR (P = 0.009) scores. Double immunofluorescence revealed Hsp72-p63 and Hsp72-AR co-expressions in basal cell nuclei. Aberrant cytoplasmic p63 immunolabelling was observed in 3 of 11 PCa cases. These results suggest a role of the combined expression of Hsp72, p63 and AR in basal epithelial cells in canine BPH and PCa.

Endoscopic Vascular Targeted Photodynamic Therapy with the Photosensitizer WST11 for Benign Prostatic Hyperplasia in the Preclinical Dog Model

Vascular targeted photodynamic therapy with WST11 (TOOKAD® Soluble) is in phase III clinical trials of an interstitial transperineal approach for focal therapy of prostate cancer. We investigated the safety and efficacy of the endourethral route in the context of benign prostatic hyperplasia in the dog model. An optical laser fiber was positioned in the prostatic urethra of 34 dogs, including 4 controls. It was connected to a 753 nm diode laser at 200 mW/cm fluence, delivering 200 to 300 J. WST11 (5 to 15 mg/kg) was infused intravenously in 2 modes, including continuous, starting 5 to 15 minutes before and during illumination, or a bolus 5 to 10 minutes before illumination. Prostate ultrasound, cystourethrogram, urodynamics and histopathology were performed. Followup was 1 week to 1 year. Endourethral WST11 vascular targeted photodynamic therapy was uneventful in all except 1 dog, which experienced urinary retention but reached the 1-week end point. All prostates except those in controls showed hemorrhagic lesions. They consisted of 2 levels of concentric alterations, including periurethral necrosis with endothelial layer destruction and adjacent inflammation/atrophy with normal blood vessels. Prostatic urethral width increased as early as 6 weeks after treatment, while prostatic volume decreased, reaching 25% by 18 to 26 weeks. A parallel decrease in urethral pressure at 6 weeks lasted up to 1 year. We confirmed the vascular effect of endourethral WST11 vascular targeted photodynamic therapy. To our knowledge we report for the first time that the resulting periurethral necrosis led to significant, sustained widening of the prostatic urethra, accompanied by long-term improvement in urodynamic parameters. These findings support future clinical applications of this minimally invasive approach to benign prostatic hyperplasia.

Testicular Steroids, Prolactin, Relaxin and Prostate Gland Markers in Peripheral Blood and Seminal Plasma of Normal Dogs and Dogs with Prostatic Hyperplasia

Concentrations of 17β-oestradiol (E(2) ), testosterone (T), 5α-dihydrotestosterone, prolactin (PRL) and relaxin (RLN) were determined in peripheral blood serum or plasma and prostatic secretion of 77 physically healthy intact male dogs (19 Rhodesian Ridgebacks/RR, 58 dogs of other breeds, 1-9 years of age). Furthermore, the concentrations of acid phosphatase in prostatic secretion and canine prostate-specific esterase (CPSE) were measured in blood plasma. All dogs were submitted to a complete breeding soundness examination, including B-mode sonography. Prostatic volume was larger, and blood plasma levels of CPSE were higher in ageing dogs and in dogs with benign prostatic hyperplasia (BPH) compared with young dogs and dogs with normal prostate. Furthermore, a higher E(2) /T ratio was found in dogs with BPH. Despite missing significant differences in PRL concentrations, the slight increases in PRL concentrations in the prostatic secretion observed both with increasing age and in dogs with BPH and the observed correlations between concentrations of PRL and testicular steroids may possibly indicate a role of PRL in the pathogenesis of canine BPH. Serum RLN concentrations were at similar level in all dogs. Regarding breed differences, an appreciably larger prostatic volume and higher concentration of CPSE were verified in RR than in other pure-bred dogs, confirming our suspicion of a premature enlargement of the prostate gland, which may result from a genetic disposition for BPH in this breed.

Validation of a Model to Develop a Symptom Index for Benign Prostatic Hyperplasia in Dogs

Benign prostatic hyperplasia (BPH) is a spontaneous and age-related condition in humans and intact male dogs. A symptom index for BPH in men was created by the American Urological Association. In this study, it has been developed and statistically validated as a model to assign an objective score to canine BPH severity based on clinical signs observed and/or subjectively reported to the veterinarian by dog owners. The medical records of the Animal Reproduction Unit of University of Bologna (Italy) were used to select dogs with a clinical diagnosis of BPH. A data set was built up, and the animals were included in the statistical analysis as dependent variables. A score of 1-3 was assigned to the disease severity of each case based on signs annotated, graded using a scale ranging from 1 to 4. Signs of BHP were entered as predictors while disease severity as dependent variable to generate the predictive model. The model was finally used to re-classify each case of the data set, and the percentage of corrected predictions calculated. Overall, 373 subjects were entered in the model. Between them, 243, 107 and 23 animals have been represented based on medical records with a BPH severity score of 1, 2 and 3, respectively. The model correctly predicted the response variable in 97.3% of the cases. In this study, a BPH symptom index was created for the first time in dogs, which may be useful to standardize BPH severity with an objective score and to evaluate the necessity, the kind and the effectiveness of treatment.

5-Lipoxygenase expression in benign and malignant canine prostate tissues*

5-Lipoxygenase (5-LO) is overexpressed in human prostate carcinomas (PCs), and its inhibition decreases proliferation and induces apoptosis in prostate cancer cell lines. We hypothesized that 5-LO would be overexpressed in canine PC compared with benign prostate tissue and may be important in the pathogenesis of the disease. Immunoblot analysis of canine PC and benign prostatic hyperplasia (BPH) tissues demonstrated 5-LO expression in both. 5-LO immunohistochemical staining was not significantly different within the stromal or epithelial components of canine primary PC, BPH or suppurative prostatitis, suggesting that differential expression of this enzyme does not occur in these conditions. The percentage of tumour cells expressing 5-LO was significantly lower in metastatic PC lesions compared with primary PC (P < 0.0001). This decreased expression may indicate down-regulation or altered expression of the enzyme with progression of canine PC to a metastatic phenotype.

Temporary Placement of a Covered, Retrievable, Barbed Stent for the Treatment of Hormone-induced Benign Prostatic Hyperplasia: Technical Feasibility and Histologic Changes in Canine Prostates

To evaluate the technical feasibility of a covered, retrievable, barbed prostatic stent and to determine stent-induced histologic changes of the prostate in canine benign prostatic hyperplasia (BPH). BPH was induced in 8 male beagles by administration of dihydrotestosterone and beta-estradiol. Under fluoroscopy guidance, covered, retrievable, barbed stents were placed in the prostatic urethras. Urethrograms were obtained every three to 4 weeks until sacrifice. The stents were removed 8 weeks after placement. The dogs were sacrificed immediately (group A, n = 4) and 8 weeks after stent removal (group B, n = 4). Histologic changes of prostates were microscopically evaluated. Stent placement was technically successful in all dogs. The diameters of the prostatic urethra were 14.1 mm + or - 0.5 and 13.7 mm + or - 0.5 on urethrograms obtained immediately after and 8 weeks after stent removal (P = .268). Stent removal was successful in all dogs except one, in which the stent was obstructed by stone formation. Small sandy stones were identified attached to the removed stents of two dogs. Histologic examination revealed extensive prostatic glandular atrophy involving 95.1% + or - 2.2 (group A) and 94.5% + or - 2.4 (group B) of entire prostate (P = .773). A covered, retrievable, barbed prostatic stent seems to be feasible for use in hormone-induced canine BPH. The stent induced prostatic urethral dilatation, and extensive prostatic glandular atrophy persisted up to 8 weeks after stent removal.

COMPARISON OF HISTOLOGICAL COMPOSITIONS AND APOPTOSIS IN CANINE SPONTANEOUS BENIGN PROSTATIC HYPERPLASIA TREATED WITH ANDROGEN SUPPRESSIVE AGENTS CHLORMADINONE ACETATE AND FINASTERIDE

Chlormadinone acetate and finasteride are androgen suppressive agents clinically used for benign prostatic hyperplasia but their mechanism for inducing prostatic atrophy differs. We investigated the effect of these androgen suppressive agents on prostatic histology and apoptosis using the spontaneous canine benign prostatic hyperplasia model. Animals were treated with oral chlormadinone acetate or finasteride for 25 weeks. The prostatic volumes were analyzed every 5 weeks. Prostatic androgen and estrogen concentrations, histological composition and apoptosis were determined at the end of treatment. Apoptosis was measured by in situ labeling of 3' hydroxy ends of the DNA breaks using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling method. There was a similar volume reduction effect with 0.3 mg./kg. chlormadinone acetate daily and 1 mg./kg. finasteride daily. Chlormadinone acetate decreased testosterone and dihydrotestosterone but finasteride decreased only dihydrotestosterone in the prostate gland. The concentration ratio of estradiol-to-total androgen in the prostate was significantly increased in finasteride treated canines. Chlormadinone acetate and finasteride decreased the epithelial and stromal components. The extent of apoptosis observed in the prostate was significantly higher in the chlormadinone acetate group compared to that of the control and finasteride groups. Although a similar effect of chlormadinone acetate and finasteride was observed in the induction of prostatic regression and composition of the histological components, the sustained increase in apoptosis was observed only in chlormadinone acetate treated canines. We suggest that different intraprostatic endocrine environments created by chlormadinone acetate or finasteride, which have different intraprostatic testosterone levels and estradiol-to-androgen ratios, may be responsible for the different outcomes in the extent of apoptosis.

The effects of chlormadinone acetate (CMA), antiandrogen, on the pituitary, testis, prostate and adrenal gland of the dog with spontaneous benign prostatic hyperplasia.

The effect of chlormadinone acetate (CMA), a synthetic steroidal antiandrogen, on spontaneous benign prostatic hyperplasia (BPH) in dogs was investigated. Male beagle dogs (5-8 years old) were divided into four experimental group. Group 1 consisted of untreated controls. Groups 2 and 3 received CMA 0.03 and 0.1 mg/kg/day, p.o., respectively, for 6 months. In group 1, glandular hyperplasia of the prostate was clearly detected. The glandular epithelial cells showed uniformly intense nuclear staining for androgen receptor (AR). AR was also localized in the nuclei of the fibro-muscular stromal cells. In groups 2 and 3, CMA produced marked atrophy of the glandular epithelium. The interacinar fibro-muscular stroma was prominent. The nuclear staining for AR in both epithelial and stromal cells was remarkably decreased. In addition, a histopathological study showed that CMA medication for 6 months exerted no effect on the testes and adrenal glands or on immunoreactive positive cells to LH- and ACTH-antibody (pituitary LH- and ACTH-cells). Therefore, it is concluded that CMA (0.03 and 0.1 mg/kg) causes regression of spontaneous canine BPH without any histopathological effects on the testes, adrenal glands or pituitary LH- and ACTH-cells.