Injection Of Testosterone Propionate Research Articles

Preventive Effects of Lignan Extract from Flax Hulls on Experimentally Induced Benign Prostate Hyperplasia

Consumption of diet rich in lignans may decrease the risk of some chronic hormonal conditions such as benign prostatic hyperplasia (BPH). This study investigated whether a lignan-rich extract from flaxseed hulls, LinumLife EXTRA (LLE), could prevent BPH using the testosterone propionate (TP)-induced BPH rat model. Male Wistar-Unilever rats were randomly divided into four groups of 12 rats each: a negative control group fed with control diet and receiving daily subcutaneous injections of corn oil without TP, and three groups fed with control diet (positive control), diet containing 0.5% LLE (LLE 0.5) or 1.0% LLE (LLE 1.0) and receiving daily subcutaneous injections of TP in corn oil. Treatments with diets started 2 weeks before the induction of BPH and were carried out for 5 consecutive weeks. The influence of TP and LLE on body weight (BW), food and water consumptions, and enterolactone (ENL) levels in serum and urine of rats was examined at the end of the 5-week treatment period. TP significantly diminished the mean body weight gain (MBWG) of positive control rats and their food and water consumptions while LLE reduced significantly this MBWG reduction in a dose-dependent manner. The lignan-rich extract significantly inhibited TP-induced prostate size ratio (prostate weight/rat BW) increase in comparison with positive controls (P<.001). This effect was dose dependent. Higher serum and urine levels of ENL correlated well with the dose of extract provided to rats. It was concluded that the lignan-rich flaxseed hull extract prevented the TP-induced BPH indicating it might be beneficial in the prevention of BPH.

Administration of an anabolic steroid during the adolescent phase changes the behavior, cardiac autonomic balance and fluid intake in male adult rats

Few data are available on adolescent users because most behavioral studies on anabolic–androgenic steroids (AAS) abuse have been performed in adults. Studies evaluating the impact of long-term effects of AAS abuse on the prepubertal phase are even more uncommon. Accordingly, this study was developed to test the hypothesis that changes induced by the use of AAS during the adolescent phase may be noted in the adult phase even when the AAS treatment cycle is discontinued. Therefore, not only behavioral changes but also possible autonomic and electrolyte disorders were evaluated. For this purpose, we used male prepubertal, 26-day-old (P26) Wistar rats that were treated with vehicle (control, n=10) or testosterone propionate (TP; 5mg/kg intramuscular (IM) injection, AAS, n=10) five times per week for 5weeks, totaling 25 applications during the treatment. Aggression tests were performed at the end of the cycle (P54–56), whereas open-field tests (OFTs), elevated plus maze (EPM) behavioral tests and measurements of heart rate variability (HRV), fluid intake and pathology were conducted in the adult phase (P87–92). The AAS group showed greater aggressiveness in the pubertal phase and higher levels of horizontal and vertical exploration and anxiety-related behavior in the adult phase than the control group (P<0.05). HRV tests showed an increase in sympathetic autonomic modulation, and hydroelectrolytic assessment showed lower basal intake levels of hypertonic saline than the control group (P<0.05), without statistically significant changes in the basal intake of water. These data together suggest that the use of AAS during the prepubertal phase induces behavioral, autonomic and hydroelectrolytic changes that manifest in the adult phase even when treatment is discontinued in late adolescence in rats.

Intervention effect and mechanism research of total flavonoid of Pteris multifida in benign prostatic hyperplasia rats

Objective Research the intervention effect of total flavonoid of Pteris multifida in benign prostatic hyperplasia(BPH) castrated rats and the possible mechanism.Methods Removing of bilateral testes in SD rats,and subcutaneous injecting of testosterone propionate,established castrated rat model of benign prostatic hyperplasia.After the success of modeling,The model rats were randomly divided into 6 groups,the blank control group,model group,total flavonoid of Pteris multifida group (high,medium,low dose group),positive drug group (dutasteride group,prostat group),were fed with relevant drugs respectively,blank control group and model group were fed with the same volume of distilled water.Every group was given daily administration and consecutive for 45 days,then weighed the prostate and calculated the prostatic index (PI),measured the level of serum testosterone (T),dihyrotestotestosterone (DHT),estradiol (E2).Observe the pathological changes at the prostate tissue under the light microscope,observe the ultrastructural changes of prostate cells under the electron microscope.Results Total flavonoid of Pteris multifida can reduce the prostate wet weight and PI,Compared with rats in the BPH model group [(2.284 ±0.241) g,(0.586 ±0.100)％],total flavonoid of Pteris multifida treated groups had remarkably lower prostate wet weight [(1.750 ± 0.245),(1.998 0.328),(2.064 ± 0.196) g] and PI [(0.440 ± 0.069),(0.481 ± 0.085),(0.519 ± 0.063) ％],except the PI of low dose group,the difference between groups was statistically significant (P ＜ 0.05).The levels of T,E2 and DHT were determined via enzyme linked immunosorbent assay (ELISA).Compared with rats in the BPH model group [(0.21-±0.02) μg/L,(18.4 ± 1.65) ng/L),total flavonoid of Pteris multifida high dose treated group had remarkably lower T and DHT levels [(0.18 ±0.01) μg/L,(16.3 ± 1.61) ng/L],however and the ratio of E2/T in high dose group (7.24 ± 0.63) had increased compared with rats in the BPH model group (6.53 ± 0.35),the difference between groups was statistically significant (P ＜ 0.05).The pathological manifestations improved with various degrees.Observation with electron microscopic each dose group of total flavonoid of Pteris multifida showed low columnar epithelial cells,the nucleolus fiat,nucleus atrophy and apoptosis.Conclusion This study showed that subcutaneous injection of testosterone propionate could replicate of the model of BPH in rats successful.The total flavonoids of Pteris multifida could significantly reduce the prostate wet weight and PI.The mechanism might be total flavonoid of Pteris multifida could reduce T and DHT levels,increase E2/T ratio.maintain the estrogen and androgen in relative balance along with promote the apoptosis and regulate the cell cycle,so as to the treatment effect of inhibiting hyperplasia. Key words: Benign prostatic hyperplasia; Pteris multifida; Total flavonoids; Sex hormone; Apoptosis

Chronic testosterone propionate supplement could activated the Nrf2-ARE pathway in the brain and ameliorated the behaviors of aged rats

Aging is usually associated with a progressive disruption of the redox balance leading to recurrent damage resulting from oxidative stress. Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of motor behavior disorders. Therefore, antioxidant therapies have received considerable attention in motor behavior defects treatment. The nuclear factor erythroid 2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) to induce antioxidant and phase II detoxification enzymes under conditions of oxidative stress, which reduces oxidative stress and accumulation of toxic metabolites. Testosterone has many physiological and behavioral effects throughout the lifespan and shown to affect motor behavior in adult male rats and gonadectomized rats. However, whether Nrf2-ARE pathway is activated after testosterone administration has not been studied in aged rats. The tilting-plane test and the horizontal-wire test as well as the oxidative stress parameters, the expression of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase-1 (NQO1) and the number of tyrosine hydroxylase immunoreactive (TH-ir) cells in brain were examined in aged rats following chronic subcutaneous injections of testosterone propionate (TP). Our study showed that chronic TP supplement significantly ameliorated the decline of balancing reactions and muscular strength associated with aging. Oxidative stress parameters were ameliorate, the expression of Nrf2, HO-1 and NQO1 at protein or gene levels and the number of TH-ir cells significantly increased in substantia nigra or caudate putamen after TP treatment in aged rats. Our findings demonstrated that chronic TP treatment activated Nrf2-ARE pathway may influence the maintenance of the balancing reactions and muscular strength and reduce TH-ir cells death in aged rats. Therefore, TP supplement have shown for therapeutic strategies in the treatment and modification of motor behavior disorders.

The Pancreas Is Altered by In Utero Androgen Exposure: Implications for Clinical Conditions Such as Polycystic Ovary Syndrome (PCOS)

Using an ovine model of polycystic ovary syndrome (PCOS), (pregnant ewes injected with testosterone propionate (TP) (100 mg twice weekly) from day (d)62 to d102 of d147 gestation (maternal injection – MI-TP)), we previously reported female offspring with normal glucose tolerance but hyperinsulinemia. We therefore examined insulin signalling and pancreatic morphology in these offspring using quantitative (Q) RT-PCR and western blotting. In addition the fetal pancreatic responses to MI-TP, and androgenic and estrogenic contributions to such responses (direct fetal injection (FI) of TP (20 mg) or diethylstilbestrol (DES) (20 mg) at d62 and d82 gestation) were assessed at d90 gestation. Fetal plasma was assayed for insulin, testosterone and estradiol, pancreatic tissue was cultured, and expression of key β-cell developmental genes was assessed by QRT-PCR. In female d62MI-TP offspring insulin signalling was unaltered but there was a pancreatic phenotype with increased numbers of β-cells (P<0.05). The fetal pancreas expressed androgen receptors in islets and genes involved in β-cell development and function (PDX1, IGF1R, INSR and INS) were up-regulated in female fetuses after d62MI-TP treatment (P<0.05–0.01). In addition the d62MI-TP pancreas showed increased insulin secretion under euglycaemic conditions (P<0.05) in vitro. The same effects were not seen in the male fetal pancreas or when MI-TP was started at d30, before the male programming window. As d62MI-TP increased both fetal plasma testosterone (P<0.05) and estradiol concentrations (P<0.05) we assessed the relative contribution of androgens and estrogens. FI-TP (commencing d62) (not FI-DES treatment) caused elevated basal insulin secretion in vitro and the genes altered by d62MI-TP treatment were similarly altered by FI-TP but not FI-DES. In conclusion, androgen over-exposure alters fetal pancreatic development and β-cell numbers in offspring. These data suggest that that there may be a primary pancreatic phenotype in models of PCOS, and that there may be a distinct male and female pancreas.

496 – Proteomic changes in the hypothalamus of female rats injected exogenous androgen before sexual differentiation

Objective In this study, we aimed to identify protein molecules in the hypothalamus in the female rats injected exogenous androgen before sexual differentiation. Methods Neonatal female SD rats were randomly divided into two groups: experimental group and control female group. Four neonatal male SD rats were control male group. All animals were subjected to intraperitoneal injection of testosterone propionate as experimental group or aseptic oil as control. The rats were sacrificed 90 days after the injection and the brains were collected. 2-DE were performed in order to establish profiles of proteome from rat hypothalamus and followed by MALDITOF- TOF mass spectrometry was used to identify proteins differentially expressed in rat hypothalamus from experimental group as compared to normal control group. Results 11 differential spots were cut off from the Silver stained gel, and 9 of the spots were identified, which were Dihydropyrimidinase-like 3 (DPYSL3), heterogeneous nuclear ribonucleoprotein K(hnRNP K), Profilin2, Triosephosphate isomerase 1(Tpi 1), Carbonic anhydrase II(CA II), Annexin A3, Protein disulfide isomerase associated 3 (PDIA3), Creatine kinase-B and Secernin 1. Conclusion The results of the present study indicate that the development of sexual differentiation may be associated with the alteration in the expression of a large number of cytosolic proteins in the hypothalamus.

Inhibitory effects of crude polysaccharides from semen vaccariae on benign prostatic hyperplasia in mice

Ethnopharmacological relevanceSemen vaccariae, the seeds of Vaccaria Segatalis, is a famous traditional herb for the treatment of stranguria disease, e.g. benign prostatic hyperplasia (BPH). The present study investigated the effect of crude polysaccharide from Semen vaccariae (SVCP) on BPH in mice in order to further understand the efficacy substance of this medicinal plant. Materials and methodsSixty healthy adult male Kunming mice were randomly divided into five groups with 12 mice for each group: sham-operated group, BPH model group; BPH model group treated with Pule'an at a dose of 1.20g/kg; BPH model group treated with SVCP at dose levels of 1.67g/kg and 0.42g/kg. The drugs were administered orally once a day consecutively for 12 days. The BPH in mice was created by subcutaneous injection of testosterone propionate for 5mg/(kgd) to the uncastrated mice once a day consecutively for 12 days. The inhibitory effects on BPH of SVCP were evaluated by prostatic index, testicular index and histopathologic examination. ResultsComparing with BPH model group, BPH mice fed with SVCP exhibited significant differences in both the prostatic index and testicular index. On the aspect of histopathology, the SVCP treated BPH mice exhibited similar histological aspects observed in the mice of sham group while the BPH mice exhibited typical features of prostate glandular hyperplasia. ConclusionsSVCP exhibited a significant inhibitory activity on BPH by reducing the prostatic index, testicular index, and ameliorating the pathomorphology. The results indicated that the polysaccharide should be the main efficacy substance of Semen vaccariae and may contribute, in a large part, to Semen vaccariae's traditional medicinal use for the treatment of stranguria disease.

Effects of Platycodon grandiflorum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Benign prostatic hyperplasia (BPH) is highly prevalent in the male population over the age of 60 years, manifesting as prostatic enlargement and distinctive changes in tissue histomorphology. In this study, we investigated whether a Platycodon grandiflorum methanolic extract (PGME) improved BPH in a testosterone propionate (TP)-induced model of BPH in rats. Castration was performed via the scrotal route under sodium pentobarbital anesthesia, and BPH was induced in the rats with a subcutaneous injection of TP (3 mg/kg) given every consecutive day for 4 weeks after castration. The control group of castrated rats received subcutaneous injections of corn oil. Experimentally, induced rat model of BPH, PGME led to significant reductions in prostate weight and dihydrotestosterone levels in the serum and prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and PGME treatment significantly reduced the severity of the lesion. Therefore, PGME was effective in reducing TP-induced BPH in a rat model, and may be useful for the clinical treatment of patients with BPH.

Epididymosome‐Mediated Acquisition of MMSDH, an Androgen‐Dependent and Developmentally Regulated Epididymal Sperm Protein

A differential proteomics approach led to the identification of several novel epididymal sperm proteins. One of the novel proteins was methylmalonate-semialdehyde dehydrogenase (MMSDH). In the present study, we carried out an in-depth characterization to study its regulation by androgen, its appearance during ontogeny, and the mechanism of its interaction with and acquisition by the sperm. Western blotting and immunohistochemical studies suggest that the protein is present in both tissue and sperm from all regions of the epididymis, indicating synthesis as well as acquisition of the protein in these regions. Androgen depletion resulted in reduction of the MMSDH protein level in the epididymis, which completely disappeared 1 week after castration. The protein reappeared after testosterone propionate injection, indicating that the protein is regulated by androgens. Ontogeny studies indicated that the protein appeared from day 10 postnatal with a gradual increase at day 30, which maximized at day 50, indicating that the protein is developmentally regulated and is probably involved in epididymal development. Sequential extraction of sperm proteins indicated that MMSDH exists both as a peripheral and integral form on the plasma membrane. We also found that the protein can be transferred from the epididymosomes to testicular sperm in vitro. The study provides evidence regarding the acquisition of this multidomain androgen and developmentally regulated protein in the epididymis via the epididymosomes. The molecule has generated enough interest and deserves to be investigated further for its physiological relevance.

Inhibitory effect of Yukmijihwang-tang, a traditional herbal formula against testosterone-induced benign prostatic hyperplasia in rats

BackgroundYukmijihwang-tang, a traditional herbal formula, has been used for treating disorder, diabetic mellitus and neurosis in China (Liu-wei-di-huang-tang in Chinese), Japan (Lokumijio-to in Japanese) and Korea for many years. In this study, we investigated the effects of Yukmijihwang-tang water extract (YJT) on the development of benign prostatic hyperplasia (BPH) using a rat model of testosterone propionate (TP)-induced BPH.MethodsA total of 30 rats were divided into five groups. One group was used as a control and the other groups received subcutaneous injections of TP for 4 weeks to induce BPH. YJT (200 or 400 mg/kg) was administered daily for 4 weeks to two groups by oral gavage concurrently with the TP. The animals were euthanized, the prostate and body weights were recorded, and tissues were subjected to hormone assays and histomorphology. In addition, we investigated proliferating cell nuclear antigen (PCNA) expression in the prostate using immunoblotting.ResultsAnimals with BPH showed significantly increased absolute and relative prostate weights, increased dihydrotestosterone levels in the serum or prostate and increased PCNA expression in the prostate; however, YJT-treated animals showed significant reductions compared with the animals with TP-induced BPH. Histomorphology also showed that YJT inhibited TP-induced prostatic hyperplasia.ConclusionsThese findings indicate that YJT effectively inhibited the development of BPH and might be a useful drug clinically.

Jaeumganghwa-tang, a traditional herbal formula inhibits the development of benign prostatic hyperplasia in rats

Benign prostate hyperplasia (BPH) is the most common proliferative disorder affecting older men and results in prostate enlargement and lowered urinary tract symptoms. Jaeumganghwa-tang (JGT), an oriental traditional herbal formula, has been used in China (Zi-yin-jiang-huo-tang in Chinese), Japan (Jiin-koka-to in Japanese), and Korea for many years. Effects of JGT on prostate dihydrotestosterone (DHT) level and prostatic hyperplasia were investigated using a rat model, in which BPH was induced using testosterone propionate (TP). Rats were divided into five groups. One group was used as a normal, and four groups received subcutaneous injections of TP for 4 weeks to induce BPH. JGT (200 or 400 mg/kg) was administered daily for 4 weeks by oral gavage concurrently with TP injections, and rats were sacrificed at scheduled times. Prostates were weighed, and histopathologic examination was conducted. DHT levels in serum and the prostate were measured, and the expression of proliferating cell nuclear antigen (PCNA) protein was investigated using Western blotting. BPH animals showed increases in absolute and relative weights of the prostate, levels of DHT in serum and the prostate, and expression of PCNA in the prostate, whereas JGTtreated animals showed significant reductions in these indices compared with the BPH animals. Administration of JGT attenuated TP-induced epithelial hyperplasia. These findings indicate that JGT inhibits the development of BPH, an effect closely associated with a reduction in DHT level.

Markers associated with testosterone enhancement of methamphetamine-induced striatal dopaminergic neurotoxicity

Intact male CD-1 mice received an injection of testosterone propionate (TP – 5 ug), progesterone (P – 5mg), the oil vehicle or remained untreated (control). At 24 hours after hormonal treatments the mice received an injection of methamphetamine (MA - 40mg/kg) and rectal temperatures were measured. At 5days post-MA, assays were performed to assess effects of these treatments. Maximal increases in body temperatures, that were significantly greater than oil-treated controls, were obtained in TP-treated mice. At 5days post-MA, maximal weight reductions were obtained with TP-treated mice, while P-treated mice showed no significant decrease between the pre- versus post-MA determinations. Striatal dopamine concentrations showed maximal reductions and heat-shock protein-70 maximal increases in the TP group, with both differing significantly as compared with all other groups. Protein levels of dopamine transporters were significantly decreased in P-treated mice, while vesicular monoamine transporter-2 was significantly decreased in TP-treated mice. Taken together, these results suggest that testosterone exacerbates the deleterious effects of MA within male mice as indicated by a number of markers related to neurotoxicity. The changes in markers as associated with this enhanced neurotoxicity suggest that TP may increase thermal/energy responses and/or oxidative stress to produce this effect.

Ursolic acid reduces prostate size and dihydrotestosterone level in a rat model of benign prostatic hyperplasia

Benign prostatic hyperplasia (BPH) is characterized by hyperplasia of prostatic stromal and epithelial cells, which can lead to lower urinary tract symptoms. The prevalence of BPH increases in an age-dependent manner. We investigated the protective effect of ursolic acid in BPH development using a testosterone-induced BPH rat model. BPH was induced in experimental groups by daily subcutaneous injections of testosterone propionate (TP), for a period of four weeks. Ursolic acid was administrated daily by oral gavage at a dose level of 5mg/kg during the four weeks of TP injections. Animals were sacrificed on the scheduled termination, before prostates were weighed and subjected to histopathological examination. TP and dihydrotestosterone (DHT) levels in the serum and prostate were also measured. BPH-induced animals displayed an increase in prostate weight with increased testosterone and DHT levels in both the serum and prostate. However, ursolic acid treatment resulted in significant reductions in prostate weight and testosterone and DHT levels in both the serum and prostate, compared with BPH-induced animals. Histopathological examination also showed that ursolic acid treatment suppressed TP-induced prostatic hyperplasia. These findings indicate that ursolic acid may effectively inhibit the development of BPH and it may be a useful agent in BPH treatment.

Effects of Melandrium firmum methanolic extract on testosterone-induced benign prostatic hyperplasia in Wistar rats

Benign prostatic hyperplasia (BPH) is an age-related disease of unknown aetiology characterized by prostatic enlargement coincident with distinct alterations in tissue histomorphology. Instead of therapeutic agents that can cause severe side effects, plant extracts are frequently used to treat BPH. In this study, we investigated whether the Melandrium firmum methanolic extract (MFME) improves BPH, using the testosterone propionate (TP)-induced BPH rat model. Castration was performed via the scrotal route under sodium pentobarbital anaesthesia. BPH in castrated rats was generated via daily subcutaneous injections of TP (3 mg kg(-1)) dissolved in corn oil, for 4 weeks. MFME was administered daily by oral gavage at a dose of 200 mg kg(-1) for 4 weeks, along with the TP injections. The control group received injections of corn oil subcutaneously. At the scheduled termination of the experiment, all rats were killed and their prostates weighed; the relative prostate weight (prostate/body weight ratio) was calculated, and histomorphological changes in the prostate were examined. Additionally, we measured the levels of testosterone and dihydrotestosterone (DHT) in the serum and the prostate. Experimentally induced BPH led to marked decreases in the relative prostate weight and the DHT levels in the serum and the prostate. Histologically, BPH was evident in the ventral lobe of the prostate, and MFME treatment suppressed the severity of the lesions. These results indicate that MFME effectively inhibits the development of BPH induced by testosterone in a rat model. Further studies will be needed to identify the compound(s) responsibility for inducing the protective effect against BPH and determine its mechanism of action.

Amelioratory effects of testosterone propionate supplement on behavioral, biochemical and morphological parameters in aged rats

Testosterone has been shown to affect motor behavior and nigrostriatal dopaminergic (NSDA) system in young and adult male rats. However, it is not known whether exogenous testosterone intervention to aged male rats can ameliorate age-related motor impairment. Thus, in the present study, the open field motor behavior and adhesive tape removal motor performance as well as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) of NSDA system were examined in aged male rats following chronic subcutaneous injections of testosterone propionate (TP). Aged rats showed significantly reduced open field motor behavior and adhesive tape removal motor performance compared to adult rats. Chronic TP supplement significantly ameliorated the age-related motor deficits. The expression of TH and DAT of NSDA system was significantly enhanced in TP-treated aged rats revealed by RT-PCR, Western blot and immunohistochemistry analysis respectively. The results imply that chronic TP treatment may favorably improve the declined motor behavior and motor performance with aging. Testosterone propionate supplement that facilitated NSDA system may influence the maintenance of motor behavior and performance in aged rats.

Testosterone and social isolation influence adult neurogenesis in the dentate gyrus of male rats

Testosterone has been previously shown to enhance adult neurogenesis within the dentate gyrus of adult male rats, whereas social isolation has been shown to cause a decrease in adult neurogenesis under some conditions. The current study tested the combined effects of testosterone and social isolation upon adult neurogenesis using two experiments involving adult male rats. For both experiments, half of the subjects were pair-housed and half were housed individually for the duration of the experiments (34 days). For experiment 1, the subjects were divided into four groups (n=8/group): (1) sham/pair-housed, (2) sham/isolated, (3) castrate/pair-housed, and (4) castrate/isolated. Rats in the castrate groups were bilaterally castrated, and rats in the sham groups were sham castrated. For experiment 2, all rats were castrated, and the effects of testosterone were tested using daily injections of testosterone propionate (0.500 mg/rat for 15 days) or the oil vehicle. Subjects were divided into four groups (n=8/group): (1) oil/pair-housed, (2) oil/isolated, (3) testosterone/pair-housed, and (4) testosterone/isolated. All rats were injected with 5-bromo-2'-deoxyuridine (BrdU, 200 mg/kg body mass), and immunohistochemistry was used to determine levels of neurogenesis following a 16-day cell survival period. For experiment 1, castrated subjects had significantly fewer BrdU-labeled cells along the granule cell layer and subgranular zone (GCL+SGZ) of the dentate gyrus than did intact subjects, and this effect was mainly due to low levels of neurogenesis in the castrate/isolated group. For experiment 2, social isolation caused a significant decrease in neurogenesis within the GCL+SGZ relative to the pair-housed groups. Testosterone injections did not buffer against this effect but instead tended to cause a decrease in neurogenesis. Thus, social isolation reduced hippocampal neurogenesis, but the effects of testosterone were inconsistent. This suggests that normal circulating levels of testosterone may buffer against the neurogenesis-impairing effects of isolation, whereas high doses of testosterone do not.

Effects of Androgen on the Expression of Vascular Endothelial Growth Factor in the Penile Corpus Cavernosum

To investigate the effect of orchiectomy and androgen replacement on the expression of vascular endothelial growth factor (VEGF) in rat penile tissue. Adult male Sprague-Dawley rats (12 weeks old) were left intact (control) or surgically castrated. Orchiectomized rats were left untreated or received testosterone propionate (TP) for 7 days, beginning 1 or 2 weeks after castration. Erectile function was assessed by measuring intracavernosal pressure in response to cavernous nerve stimulation, and the expression of VEGF protein and mRNA was determined by immunohistochemistry, Western blot analysis, and reverse transcriptase-polymerase chain reaction. Serum testosterone values were measured in each animal by radioimmunoassay. Serum androgen levels decreased significantly in castrated animals, whereas TP injection normalized the serum levels of testosterone. Intracavernosal pressure was significantly decreased in untreated castrated rats (31.3 ± 15.7% at 2 weeks postcastration; 18.6 ± 4.6% at 3 weeks postcastration) compared with intact controls (58.0 ± 11.4% and 58.9 ± 8.2%, respectively). Erectile function was normalized in androgen-replaced rats, irrespective of treatment was initiation 1 or 2 weeks after orchiectomy. The expression of VEGF protein and mRNA was decreased in the corpus cavernosum of castrated animals compared with controls, whereas androgen replacement normalized the expression of VEGF. These results were consistently observed by all 3 methods of assessment. These data suggest that androgen regulates the expression of VEGF in rat penile corpus cavernosum and confirms the importance of androgens in the maintenance of erectile function.

Effects of Danggui-beimu-kushen Pill on expression of PCNA, bcl-2 and bax in BPH mice model

Objective To study the effect of Danggui-beimu-kushen Pill on benign prostatic hyperplasia (BPH) and its possible mechanism. Methods BPH model mouse was produced by intraperitoneal injection of testosterone propionate. The high, medium and low dose treatment group was fed high, middle and low dose of Danggui-beimu-kushen Pill respectively, while the positive control group was fed Qianliekang liquid, 600 mg/kg. All mice were executed on the 21 day. Such values were observed as the prostate index changes, pathological changes of prostate by HE staining light microscopy and the expression changes of PCNA,bcl-2 and bax by immunohistochemistry. Results The prostate index of the treatment group was lower than the model group; the PCNA and bcl-2 expression were lower than the model group, while the bax expression was higher than the model group. Meanwhile; there is no significant difference among the treatment groups.Moreover, the difference between the treatment groups and the positive control group has no statistic meaning.Conclusion Danggui-beimu-kushen Pill can suppress BPH in mice. The mechanism may be related to the reduction expression of cell-proliferation protein PCNA and apoptosis profilin bcl-2, and the increase of bax expression. Key words: Danggui-beimu-kushen Pill; BPH

Prenatal Androgen Exposure Leads to Alterations in Gene and Protein Expression in the Ovine Fetal Ovary

Exposure of a female fetus to increased androgens in utero results in an adult phenotype reminiscent of polycystic ovary syndrome. We investigated whether prenatal androgens could directly alter the structure and function of the fetal ovary. We examined fetal ovarian cell proliferation, germ cell volume, and the expression of steroid receptors and steroidogenic enzymes. In addition, we studied the inhibitors of differentiation (Ids) and the SLIT/Roundabout developmental pathways. Female fetuses were collected from ewes treated with 100 mg testosterone propionate (TP) or vehicle control (C), twice weekly from d 60 to 70 (C = 3, TP = 6) or d 90 (C = 6, TP = 8). Female fetuses were also collected at d 70 after a single injection of TP (20 mg) or vehicle C into the fetal flank at d 60 (C = 4, TP = 8). Prenatal androgenization had no effect on fetal ovarian morphology, cell proliferation, or germ cell volume. However, there was a reduction in the expression of StAR, CYP11A, CYP17, and LHR at d 90 of gestation. There was also an increase in Id1 immunostaining at d 90 and an increase in Id3 immunostaining at d 70. Direct injection of TP into the fetus down-regulated ovarian CYP11A, estrogen receptor α and β mRNA, and ROBO1 and up-regulated CYP19, androgen receptor immunostaining, and Id3 mRNA and protein. Although at d 90 prenatal androgenization does not result in structural changes of the fetal ovary, there are functional changes that may impact on ovarian development. TP has direct actions on the fetal ovary, and these may contribute to the adult ovarian phenotype in the ovine model of polycystic ovary syndrome.

Pregnane X Receptor as a Therapeutic Target to Inhibit Androgen Activity

The androgen-androgen receptor signaling pathway plays an important role in the pathogenesis of prostate cancer. Accordingly, androgen deprivation has been the most effective endocrine therapy for hormone-dependent prostate cancer. Here, we report a novel pregnane X receptor (PXR)-mediated and metabolism-based mechanism to reduce androgenic tone. PXR is a nuclear receptor previously known as a xenobiotic receptor regulating the expression of drug metabolizing enzymes and transporters. We showed that genetic (using a PXR transgene) or pharmacological (using a PXR agonist) activation of PXR lowered androgenic activity and inhibited androgen-dependent prostate regeneration in castrated male mice that received daily injections of testosterone propionate by inducing the expression of cytochrome P450 (CYP)3As and hydroxysteroid sulfotransferase (SULT)2A1, which are enzymes important for the metabolic deactivation of androgens. In human prostate cancer cells, treatment with the PXR agonist rifampicin (RIF) inhibited androgen-dependent proliferation of LAPC-4 cells but had little effect on the growth of the androgen-independent isogenic LA99 cells. Down-regulation of PXR or SULT2A1 in LAPC-4 cells by short hairpin RNA or small interfering RNA abolished the RIF effect, indicating that the inhibitory effect of RIF on androgens was PXR and SULT2A1 dependent. In summary, we have uncovered a novel function of PXR in androgen homeostasis. PXR may represent a novel therapeutic target to lower androgen activity and may aid in the treatment and prevention of hormone-dependent prostate cancer.