estradiol-3-benzoate and Prostatic-Hyperplasia

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 (5 mg/day P.O.); dogs which received tadalafil (5 mg/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.

Topics: Androgens; Animals; Contraceptive Agents, Hormonal; Dog Diseases; Dogs; Estradiol; Gene Expression Regulation; Inflammation; Male; Oxidative Stress; Phosphodiesterase 5 Inhibitors; Prostatic Hyperplasia; Tadalafil; Testosterone

This study aimed to identify the differential expression levels of androgen receptor (AR), estrogen receptors (ERα, ERβ), and progesterone receptor (PGR) between normal prostate and benign prostatic hyperplasia (BPH). The combination of immunohistochemistry, quantitative real-time reverse transcription polymerase chain reaction, and Western blotting assay was used to identify the distribution and differential expression of these receptors at the immunoactive biomarker, transcriptional, and protein levels between 5 normal human prostate tissues and 40 BPH tissues. The results were then validated in a rat model of BPH induced by testosterone propionate and estradiol benzoate. In both human and rat prostate tissues, AR was localized mainly to epithelial and stromal cell nuclei; ERα was distributed mainly to stromal cells, but not exclusively; ERβ was interspersed in the basal layer of epithelium, but sporadically in epithelial and stromal cells; PGR was expressed abundantly in cytoplasm of epithelial and stromal cells. There were decreased expression of ERα and increased expression of PGR, but no difference in the expression of ERβ in the BPH compared to the normal prostate of both human and rat. Increased expression of AR in the BPH compared to the normal prostate of human was observed, however, the expression of AR in the rat prostate tissue was decreased. This study identified the activation of AR and PGR and repression of ERα in BPH, which indicate a promoting role of AR and PGR and an inhibitory role of ERα in the pathogenesis of BPH.

Topics: Adult; Aged; Aged, 80 and over; Animals; Cell Nucleus; Cytoplasm; Epithelial Cells; Estradiol; Humans; Male; Middle Aged; Prostate; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Receptors, Androgen; Receptors, Estrogen; Receptors, Progesterone; Reference Values; Stromal Cells; Testosterone Propionate

To investigate the effects of mepartricin, a polyene macrolide antibiotic, on estrogen-induced hyperplastic prostate and seminal vesicle (SV) growth in castrated rats.. Immature rats aged 3 weeks were castrated and left untreated for 1 week. Then, 17beta-estradiol benzoate (E(2)-BA) was subcutaneously injected at a dose of 10 microg/day twice weekly, and mepartricin was orally administered at doses of 2.5, 5 and 10 mg/kg once daily for 3 weeks. The weights and hydroxyproline contents of the prostate and SV, the activity of growth factors (GFs) in the dorsolateral prostate (DLP) and the serum estrogen level were measured. Histological examination of the prostate and SV was also performed.. Mepartricin dose-dependently suppressed the increase in the serum estrogen level, the weights and hydroxyproline contents of the DLP and SV and the elevation of GF activity in the DLP induced by E(2)-BA treatment. Histological examination also revealed that treatment with mepartricin reduced collagen accumulation and thickening of the smooth muscle layer in the DLP and SV, and proliferation of the glandular epithelium in the DLP.. These results suggest that mepartricin suppresses hyperplastic growth of the DLP and SV induced by estrogen in immature castrated rats, the underlying mechanism being a reduction in the serum estrogen level, thereby suppressing stromal cell proliferation and activation.

Topics: Animals; Anti-Bacterial Agents; Castration; Disease Models, Animal; Estradiol; Male; Mepartricin; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Seminal Vesicles; Treatment Outcome

To study the influence of androgens and estrogens on human benign prostatic hyperplasia (BPH) tissue, BPH fragments were grafted subcutaneously (s.c.) into male nude mice. Testosterone alone (group I) or in combination with 17 beta-estradiol (group III) were administered either by s.c. injections as oil suspensions or continuously by s.c. implanted steroid-containing Silastic implants (groups II and IV). Intact mice without transplants and treatment served as a control (group V). After 4 weeks of treatment, animals were exsanguinated, transplants were removed, and serum was obtained. Ninety-six percent of the BPH fragments were located; they displayed histologically typical BPH acini and stroma. In transplants of all treatment groups, the majority of secretory, as well as basal, cells displayed a proliferation comparable to the original tissue. In glandular cells of all transplants, prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) could be demonstrated immunohistochemically. Specimens removed from animals bearing testosterone implants displayed a very well preserved ultrastructure that was found less frequently in samples from injection-treated animals. Acini-bearing metaplastic epithelium were more often present in transplants treated by steroid injections and seemed to be due to lower androgen or higher estrogen serum levels. Endogenous serum testosterone levels (ng/ml +/- SD; n) were lower and more variable (i.e., higher standard deviation) in groups treated by injections (group I: 3.68 +/- 2.12; n = 5 and group III: 3.86 +/- 1.13; n = 5) and were similar to those seen in intact controls (3.93 +/- 1.62; n = 6) compared with groups treated by Silastic implants (group II: 5.11 +/- 1.14; n = 10 and group IV: 10.20 +/- 0.52; n = 4). These results indicate that by application of steroids via Silastic implants, reproducible hormone effects can be obtained on BPH tissue transplanted into male nude mice, thus providing a reliable new model system for study.

Topics: Acid Phosphatase; Aged; Animals; Drug Implants; Drug Therapy, Combination; Epithelium; Estradiol; Histocytochemistry; Humans; Injections, Subcutaneous; Male; Mice; Mice, Nude; Microscopy, Electron; Middle Aged; Prostate; Prostate-Specific Antigen; Prostatic Hyperplasia; Silicone Elastomers; Testosterone; Transplantation, Heterologous