Received Testosterone Propionate Research Articles

Effect of methanol extract of Plectranthus esculentus N.E.Br tuber and its fractions on indices of benign prostatic hyperplasia in Wistar rats

Ethnopharmacological relevanceMany ethnopharmacological properties (anti-tumor, etc.) have been credited to Plectranthus esculentus tuber but the scientific basis has not been established.Aim of the study: To evaluate the effect of methanol extract of P. esculentus tuber (MEPET) (phase 1) and its fractions (phase 2) on benign prostatic hyperplasia (BPH) in rats. Materials and methodsThe study was conducted in two phases. Phase 1, thirty-five male albino rats (6 weeks old) were divided into seven groups of five rats each: normal control (NC) received olive oil (subcutaneously) and water (orally); disease control (DC) received testosterone propionate (TP) (3 mg/kg) and water; test groups (1,2,3 and 4) received TP + MEPET at 100, 200, 400, 600 mg/kg respectively; positive control, received TP + finasteride (5 mg/70 kg). After 28 days, their relative prostate weights (RPW) and prostate specific antigen (PSA) were determined. Phase 2, thirty rats were divided into 6 groups of 5 rats each: NC received olive oil (subcutaneously daily) and dimethyl sulfoxide (DMSO) (orally); DC received TP (3 mg/kg), and DMSO; test group 1 received TP and aqueous fraction of MEPET (400 mg/kg); test group 2 received TP and methanol fraction of MEPET (400 mg/kg); test group 3 received TP, and ethyl acetate fraction of MEPET (400 mg/kg); positive control received TP and finasteride (5 mg/70 kg). After 28 days, their erythrocyte sedimentation rates, RPW, prostate levels of PSA, DHT, inflammatory, apoptotic markers and prostate histology were determined. ResultsEthyl acetate fraction of MEPET modulated most of the parameters of BPH in the rats in a manner akin to finasteride as corroborated by prostate histology. ConclusionsEFPET could be useful in the treatment of BPH.

Cleistanthins A and B Ameliorate Testosterone-Induced Benign Prostatic Hyperplasia in Castrated Rats by Regulating Apoptosis and Cell Differentiation.

Background The aging male population is at higher risk for benign prostatic hyperplasia (BPH) wherein increased proliferation of stromal and epithelial cells of the prostate is observed. In this study, we investigated the effect of cleistanthins A and B on the inhibition of testosterone-induced BPH in castrated rats. Methodology Male Wistar rats were divided into eight groups (n = 6) and surgical castration was performed. BPH was induced by the administration of testosterone propionate in corn oil at 5 mg/kg for four weeks. The control group received corn oil, and the model group received testosterone propionate. The standard treatment group received finasteride orally along with testosterone. Cleistanthins A and B at 0.3, 1, and 3 mg/kg were administered by oral gavage along with testosterone. After four weeks, rats were sacrificed, and prostates were weighed and assessed for histomorphological, inflammatory, apoptotic, and proliferative markers. Results Cleistanthins A and B decreased prostatic enlargement and histopathological abnormalities. Elevated serum dihydrotestosterone levels were lowered significantly in both the cleistanthin A andcleistanthin B groups compared to the BPH model group. Cleistanthins A and B significantly lowered the serum interleukin (IL)-1β and tumor necrosis factor-alpha inflammatory markers in the test groups. Western blot analysis revealed cleistanthin A downregulated the IL-6, signal transducer and activator of transcription 3/cyclin D1 signaling pathway. Both cleistanthins A and B upregulated the apoptotic markers caspase-3 and cleaved caspase-3, whereas the cell proliferation markers cyclin D1 and proliferating cell nuclear antigen were found to be downregulated. Conclusions Both cleistanthins A and B inhibited BPH in a rat model by apoptotic induction and impeded cell proliferation.

295 Effects of Prenatal Testosterone Excess on Puberty Attainment of First-Generation ewe Lambs

Abstract Prenatal testosterone excess causes reproductive perturbations in sheep that recapitulate those seen in women with polycystic ovary syndrome (PCOS). Obesity has a significant role in the development and severity of the PCOS phenotype. Our objective was to investigate the effects of testosterone excess from gestational days (GD) 60-90 (unlike the GD 30-90 model, these animals are not virilized) and postnatal body weight (BW) gain on puberty in first-generation ewe lambs. Pregnant Suffolk ewes received testosterone propionate (T; 100 mg) or corn oil (C) i.m. twice weekly from GD 60-90 (term=147d). Ewe lambs were weaned ~3 mo of age. Control and T lambs were assigned to gain either 0.3 kg/d (C and T-maintenance) or 0.4 kg/d (T-overfed). Maintenance diet was designed to promote optimal growth without excess fat deposition. Overfed ration was designed to achieve a BW ~30% above that of maintenance. Progesterone concentrations were measured via radioimmunoassay in blood samples collected twice weekly from ewe lambs (n=15/group) during the first breeding season. Puberty was defined as when progesterone concentrations were < 0.5 ng/mL for four consecutive samples followed by three consecutive samples ≥0.5 ng/mL. Six animals (C, n=1; T-maintenance, n=3; T-overfed, n=2) did not attain puberty during the study and puberty was assigned as last day of sampling. Average daily gain was not different among treatments (C, 0.23±0.02kg; T-maintenance, 0.25±0.01kg; T-overfed, 0.27±0.02kg). Age at puberty did not differ between groups (C, 274.6±9.9d; T-maintenance, 270.0±11.3d; T-overfed, 266.0±10.2d). Similarly, BW at puberty did not differ across treatments (C, 50.44±2.2kg; T-maintenance, 52.5±2.4kg; T-overfed, 57.3±2.5kg). In conclusion, unlike GD 30-90 exposure which advanced puberty, GD 60-90 exposure did not affect age and BW at puberty in ewe lambs. Collectively, these studies suggest that GD 30-60 is a critical developmental window in which prenatal testosterone excess advances puberty in female sheep. Research support: NIH-NICHD (R01HD099096).

Fenofibrate mitigates testosterone induced benign prostatic hyperplasia via regulation of Akt/FOXO3a pathway and modulation of apoptosis and proliferation in rats

Benign prostatic hyperplasia (BPH) is one of the most age-related health problems that commonly affect men. Regrettably, many individuals may not respond to current medical therapies or develop resistance to them. Accordingly, this study aimed to uncover how potentially fenofibrate, a lipid lowering agent, can ameliorate the induced BPH in rats. Forty rats were categorized randomly into four groups; the control group was given the vehicle (olive oil); the BPH model received testosterone propionate (20 mg/kg daily; s.c.) for 4 weeks; BPH-induced group received finasteride (10 mg/kg daily; p.o.) and BPH-induced group received fenofibrate (80 mg/kg daily; p.o.). After testosterone administration, both weight and relative weight of the prostate increased. Additionally, testosterone upregulated androgen receptor (AR), 5α-reductase gene expression and increased prostate proliferation. Histopathological examination confirmed that testosterone disrupted the histo-architecture of the prostate and caused marked hyperplasia of glands and stroma. On the other hand, fenofibrate administration reverted most hyperplastic changes of testosterone, it significantly reduced weight, relative weight of the prostate and dihydrotestosterone (DHT) level compared to BPH group. Also fenofibrate significantly decreased AR and 5α-reductase gene expression. Fenofibrate significantly suppressed ps473 Akt expression causing FOXO3a nuclear inclusion, which triggered induction of apoptosis. As well, Bax/Bcl2 ratio and caspase 3 content were significantly enhanced. Fenofibrate significantly diminished cyclin D1 immunoexpression and restored normal histo-architecture. In conclusion, this study emphasizes the preventive effect of fenofibrate in BPH rat model. This can be accredited, at least partly, to inhibiting AR and 5α-reductase expressions, the anti-proliferative, and pro-apoptotic activity of fenofibrate via modulation of Akt/FOXO3a pathway.

Effects of Exercise on Serum Inflammatory Markers and NF-kb, COX-2 mRNA Expression in Prostate of BPH-Induced Mice

PURPOSE: Benign prostatic hypertrophy (BPH) is a common finding in older men and a frequent cause of lower urinary tract symptoms. The efficacy of exercise in the management of BPH-related inflammation is not fully understood. Thus, we investigated the effects of exercise on inflammatory markers in a mouse model of BPH.METHODS: A total of 36 male C57BL/6 mice were divided into three groups; CON (sham control, n=12), BPH-CON (received testosterone propionate [TP] control, n=12), and BPH-EXE (TP+aerobic exercise group, n=12). For BPH induction, mice were castrated and testosterone propionate (3 mg/kg/day) was administered by subcutaneous injection. The exercise group was forced to run on a treadmill for 30 minutes 3 times per week for 12 weeks.RESULTS: The BPH-CON group showed significantly increased blood pro-inflammatory cytokines such as interleukin-6, -1β, and TNF-α compared with CON (p<.05). Furthermore, NF-kb and COX-2 mRNA expression were significantly increased in prostate tissue (p<.05). In contrast, the BPH-EXE group exhibited a significant decrease in IL-1β and TNF-α cytokines and NF-kb and COX-2 mRNA, but a significant increase in SOD activity when compared to the BPH-CON group (p<.05).CONCLUSIONS: These results suggest that inflammation may be an important factor for the prevention and management of BPH, and that exercise may contribute to the alleviation of inflammation in the blood and prostate tissues of men with BPH.

Anti-Oxidative Effect of Aqueous Garlic Extract (AGE) on Androgen Induced Changes in Ovaries of Prepubertal Female Rats

Objectives: It has been documented that the administration of exogenous androgens to immature female rats produces polycystic ovaries. There is a substantial reduction of antioxidants in this condition, with an elevated risk of oxidative stress. The current research is intended to evaluate these effects and to assess the protection provided by aqueous garlic extract (AGE). Methods: An experimental study conducted at University of Health Sciences, Lahore. The data was collected over a period of one month. Fifty female prepubertal rats, 21 days of age, were divided into five groups, A, B, C, D and E. Group A served as control. Group B received testosterone propionate (TP) subcutaneous for 14 days and served as disease control. Group C received testosterone propionate (TP) subcutaneous for 14 days and concomitantly Aqueous garlic extract (AGE). Group D receive testosterone propionate (TP) subcutaneous for 14 days and Aqueous garlic extract (AGE) from day 14-21. Group E received testosterone propionate (TP) subcutaneous for 14 days with no intervention till day 21. Blood samples of 50 female rats were drawn by doing cardiac puncture and clear serum was collected by centrifugation. This serum was used to assess the Catalase enzyme by using specific commercial kits. Results: The concentration and activity of catalase enzyme in the female rats with polycystic ovaries showed significant decrease as compare to the healthy controls. The involvement of antioxidants to manage the polycystic ovaries may be helpful as secondary therapy to prevent oxidative damage. Conclusion: The results showed that AGE with its antioxidative properties not only prevents the damage caused by oxidative stress, it also increased the level of serum catalase that helps to create a balance between beneficial oxidant generation and damaging oxidative stress. Key words: Androgens, immature female rats, ovaries, antioxidants, oxidative stress, aqueous garlic extract (AGE), Catalase. How to cite: Bashir.Y., Habib N. Ashraf .S. Anti-Oxidative Effect of Aqueous Garlic Extract (AGE) on Androgen Induced Changes in Ovaries of Prepubertal Female Rats. Esculapio. 2021.17(01):55-59

Ethanolic extract of Azadirachta indica ameliorates ovarian defects through phosphoinositide-3 kinase inhibition in a rat model of polycystic ovary syndrome

Objective: To assess the therapeutic potential of ethanolic extract of Azadirachta (A.) indica in rats with polycystic ovary syndrome (PCOS). Methods: Thirty-five prepubertal female Sprague Dawley rats were randomly divided into five groups with 7 animals in each group. Group 1 received 0.5% carboxy methyl cellulose orally. Groups 2 to 5 received testosterone propionate (0.2 mg/kg, s.c.) dissolved in olive oil daily for 42 days to induce PCOS. In addition, group 3 was administered with A. indica extract (100 mg/kg, 0.5% carboxy methyl cellulose orally) from the 7th to 12th week, group 4 received quercetin (100 mg/kg, 0.5% carboxy methyl cellulose orally) and group 5 received wartmannin (100 mg/kg, 0.5% carboxy methyl cellulose orally). At the end of treatment, blood was collected for biochemical evaluation. Total follicular count and uterus corpus luteum count followed by PI3K gene expression in the ovary and uterus were evaluated. Results: The ethanolic extracts of A. indica significantly reduced body weight, ovary weight and uterus weight of rats. Extracts of A. indica also significantly increased the levels of serum glucose, total cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, insulin, testosterone, and luteinizing hormone. Treatment also reduced lipid peroxidation and increased antioxidant parameters in the liver homogenates of PCOS-induced rats. Histological examination of the ovary and uterus confirmed PCOS occurrence and remission state in the PCOS-induced and treated groups, respectively. Moreover, A. indica and quercetin significantly downregulated PI3K gene expression. Histopathological results of the ovary and uterus also proved the protective role of A. indica. Conclusions: A. indica leaf extract has beneficial effects in the treatment of PCOS by downregulation of PI3K gene expression.

Protocatechuic acid ameliorates testosterone‐induced benign prostatic hyperplasia through the regulation of inflammation and oxidative stress in castrated rats

Protocatechuic acid (PA) is a polyphenol-recognized for its efficacy as an antioxidant-possesses anticancer, anti-inflammatory, antioxidant properties. The efficacy of PA in the management of benign prostatic hyperplasia (BPH) has not been investigated. Forty-two castrated rats (n = 7) were treated as follows: control (corn oil), BPH only received testosterone propionate (TP) (TP 3 mg/kg intraperitoneally), BPH + PA (TP 3 mg/kg + PA 40 mg/kg), BPH + finasteride (Fin) (TP 3 mg/kg + Fin 10 mg/kg), PA only (40 mg/kg: by gavage), and Fin only (10 mg/kg: by gavage) for 4 weeks. In BPH rats, there were significant (P < .05) increases in prostatic (250%) and organosomatic (280%) weights compared with controls. Cotreatment decreased prostatic weights by 19% (PA) and 21% (Fin). Markers of inflammation: myeloperoxidase activities increased in serum (148%) and prostate (70%), as well as nitric oxide levels serum (92%) and prostatic (95%). Proinflammatory cytokines interleukin-1β and tumor necrosis factor-α increased by 3.6- and 2.8-fold. Furthermore, prostatic malondialdehyde, superoxide dismutase, and serum total acid phosphatase increased by 97%, 25%, and 48%, respectively. Histology revealed poor architecture and severe proliferation of the prostate in BPH rats. Inflammation and oxidative stress markers, as well as the histological alteration in BPH rats, was attenuated (P < .05) upon cotreatment with PA and comparable with Fin cotreatment. These results suggest that PA mitigates oxido-inflammatory responses and restored prostatic cytoarchitecture to levels comparable with control in rats induced with BPH.

Protective effect of black mulberry (Morus nigra L.) fruit hydroalcoholic extract against testosterone-induced benign prostatic hyperplasia in rats

BackgroundFinding new agents for prevention and/or treatment of benign prostatic hyperplasia (BPH) especially from natural sources is a demanding field. ObjectivesThis study aimed to evaluate the effect of black mulberry (BM) (Morus nigra) fruit hydroalcoholic extract on the establishment of BPH in rats. Materials and methodsForty-nine adult male rats were randomly assigned into 7 equal groups: I: Sham control (SC), a sham surgery was performed. II: positive control (PC), rats were castrated and received testosterone propionate, at 10mg/kg/day S.C. for BPH induction. III: comparative control (CC), BPH was induced and the rats received finasteride at 5mg/kg/day P.O. IV–VII: (T1–T4): BPH was induced and the rats received BM extract at 25, 50, 100 and 200mg/kg/day P.O. for 4 consecutive weeks. ResultsFinasteride and/or BM extract especially at the two higher dosages, significantly affected prostate weight, prostatic index, percent of inhibition, serum and prostatic levels of dihydrotestosterone (DHT), serum prostate-specific antigen (PSA), antioxidant parameters of prostatic tissue as well as histopathological and histomorphometric parameters (epithelial thickness and acinar area) of prostate. ConclusionsBM extract has protective effects against experimentally-induced BPH in rats with regard to histopathological and biochemical parameters which may be related to its antioxidant as well as DHT reducing properties in prostatic tissue.

Gonadal hormones, but not sex, affect the acquisition and maintenance of a Go/No-Go odor discrimination task in mice

In mice, olfaction is crucial for identifying social odors (pheromones) that signal the presence of suitable mates. We used a custom-built olfactometer and a thirst-motivated olfactory discrimination Go/No-Go (GNG) task to ask whether discrimination of volatile odors is sexually dimorphic and modulated in mice by adult sex hormones. Males and females gonadectomized prior to training failed to learn even the initial phase of the task, which involved nose poking at a port in one location obtaining water at an adjacent port. Gonadally intact males and females readily learned to seek water when male urine (S+) was present but not when female urine (S−) was present; they also learned the task when non-social odorants (amyl acetate, S+; peppermint, S−) were used. When mice were gonadectomized after training the ability of both sexes to discriminate urinary as well as non-social odors was reduced; however, after receiving testosterone propionate (castrated males) or estradiol benzoate (ovariectomized females), task performance was restored to pre-gonadectomy levels. There were no overall sex differences in performance across gonadal conditions in tests with either set of odors; however, ovariectomized females performed more poorly than castrated males in tests with non-social odors. Our results show that circulating sex hormones enable mice of both sexes to learn a GNG task and that gonadectomy reduces, while hormone replacement restores, their ability to discriminate between odors irrespective of the saliency of the odors used. Thus, gonadal hormones were essential for both learning and maintenance of task performance across sex and odor type.

Echocardiographic evaluation of left ventricular mass index in children with hypospadias after hormonal stimulation with topical testosterone: A randomized controlled trial

Testosterone is often used in the preoperative period of hypospadias surgery. Previous studies have demonstrated the presence of androgen receptors in cardiac myocytes that can modulate the phenotype. The use of supraphysiological doses of androgens can lead to toxicity on the heart muscle and, in some cases, to left ventricular hypertrophy. This randomized double blind controlled clinical trial aims to evaluate the effect of topical testosterone on left ventricular mass index in boys with hypospadias. Boys with hypospadias aged 6 months to 9 years were included. Children were divided into two groups: G1 - boys who received testosterone propionate 1% ointment twice a day for 30 days, and G2 - boys receiving placebo ointment in the same regimen. All children were submitted to bi-dimensional echocardiographic evaluation to compare the left ventricular mass index, blood pressure, and body mass index before and after treatment (30 and 90 days). Levels of serum testosterone, LH, and FSH were measured. Thirty-five children were analyzed: 17 in G1 and 18 in G2. No differences were found in left ventricular mass index (left ventricular mass indexed by body surface area) prior to treatment. Left ventricular mass index was 59.21±11.91g/m2 in G1 and 55.12±8.29g/m2 in G2 (p=0.244) after 30 days of treatment, and 61.13± 11.69g/m2 in G1 and 62.84±35.99g/m2 in G2 (p=0.852) after 90 days. Serum testosterone levels were 12 (7-80) ng/dL in G1 and 5 (5-7) ng/dL in G2 (p=0.018) after 30 days of treatment, and 10 (5-11) ng/dL in G1 and 5 (4-5) ng/dL in G2 (p=0.155), after 90 days (Figure). There was a small increase in systolic blood pressure (SBP) after 30 days (83.82±7.18mmHg) in the group who receive testosterone (G1) compared with controls (77.5±6.69mmHg) (p=0.010). After 90 days, SBP levels returned to basal levels in G1 (82.35± 5.62mmHg) and in G2 (81.38±4.79mmHg) (p=0.588). Topical testosterone can be considered safe in the preoperative period of children with hypospadias with no risk of left ventricular hypertrophy. An increase in systolic blood pressure occurs while using testosterone but it is transitory, returning to normal levels after 90 days.

The effects of conjugated estrogen, raloxifene and soy extract on collagen in rat bones

ABSTRACTObjective To evaluate the action of conjugated equine estrogen, raloxifene and isolated or combined genistein-rich soy extracts on collagen fibers in the bones of oophorectomized rats.Materials and methods Seventy female rats received testosterone propionate (0.1 µg/g) on the 9th day after birth. At 6 months of age, the rats were administered the vehicle (propylene glycol, 0.5 ml/day), and ten of the rats were randomly chosen to comprise the non-oophorectomized control group (GI). The other 60 rats were ovariectomized and randomized into six groups of ten as follows: GII, vehicle; GIII, conjugated equine estrogen (CEE), 50 µg/kg/day; GIV, raloxifene (RAL), 0.75 mg/kg/day; GV, genistein-rich soy extract (GSE), 300 mg/kg/day; GVI, CEE + GSE, 50 µg/kg/day + 300 mg/kg/day; and GVII, CEE + RAL, 50 µg/kg/day + 0.75 mg/kg/day. Three months after surgery, the drugs were administered for 60 consecutive days. All rats were euthanized, and their left tibiae were removed for histological routine. The histological sections were stained with hematoxylin-eosin, and picrosirius for evaluating bone microarchitecture. Types I and II collagen fibers were analyzed by immunofluorescence. Data analysis was carried out with ANOVA and Tukey's test.Results Collagen reduction was significant in the GIII animals when compared to the other groups (p < 0.05). There was no significant difference in the thickness of collagen fibers among the groups. There was a greater quantity of type III collagen in GVI than in the other groups.Conclusion Our data indicate that conjugated equine estrogen improves bone quality because it increases the quantity of type I collagen while reducing the quantity of thin collagen fibers. In addition, the combination of CEE and raloxifene or genistein-rich soy extract is not as efficient as CEE itself to improve bone quality.

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.

Hormone therapy: a revolution in understanding prostate cancer

Until the middle of the 20th century, little knowledge of the behaviour of prostate cancer existed and awareness of its exquisite sensitivity to hormones had not been realised. The conventional understanding was that prostate cancer was an autonomous, self-perpetuating, and fatal malignant disease, the progression of which could not be changed by external manipulation. In 1941, Charles Brenton Huggins, a Canadian-born American surgeon, revolutionised our understanding of prostate cancer and irrevocably changed the approach of physicians in managing and researching the treatment of neoplastic disease in general. His pioneering work heralded the era of rational drug therapy for all cancers and earned Huggins the Nobel Prize in Physiology and Medicine in 1966. Charles Huggins graduated from Harvard Medical School (Boston, MA, USA) in 1924. In 1927, he was appointed to the surgical faculty at the University of Chicago (Chicago, IL, USA) where he became Professor of Surgery in 1936. Subsequently, in 1966, he became the second surgeon to win a Nobel Prize in Medicine, with a comment from the Nobel Committee proclaiming Huggins’ work had “already given many years of an active and useful life to patients with advanced cancer over the entire civilized world—patients who would have been lost to other forms of therapy”. Many have suggested that his ground-breaking discoveries, fi rst published in 1941, should have been acknowledged by the committee at a much earlier date. In the original study by Huggins and Hodges (his student), eight patients with metastatic disease to bone were selected from an initial group of 47 patients with prostate cancer. All eight patients underwent bilateral orchidectomy; however, before this procedure, fi ve were started on daily injections of stilboestrol or oestradiol benzoate, and three were injected with daily testosterone propionate. Serum acid-phosphatase concentrations decreased in patients who received oestrogen injection before the procedure and increased in those who received testosterone propionate. From these fi ndings, Huggins and Hodges concluded that prostate cancer was receptive to androgenic activity in the body and that metastatic prostate cancer was inhibited by eliminating circulating androgens—either by surgical orchidectomy or by administration of oestrogens. Moreover, they also showed that prostate cancer was activated by androgen injections. These fi ndings have provided the scientifi c basis for the contemporary treatment of prostate cancer. For nearly 30 years after this seminal report by Huggins and Hodges, patients with advanced prostatic carcinoma were managed either by surgical orchidectomy or oestrogens, until it was shown that treatment with oestrogens resulted in substantial thromboembolic and cardiovascular complications. This fi nding stimulated further research into alternative hormonal treatments, which culminated in the development of various antiandrogens (eg, cyproterone acetate and fl utamide) and most notably synthetic luteinising-hormonereleasing-hormone (LHRH) agonists in the 1970s. The therapeutic eff ectiveness of LHRH in achieving medical castration has yet to be surpassed. Although these hormonal treatments were originally used to manage patients with metastatic disease, androgen ablation therapy is now used in a neoadjuvant or adjuvant setting in combination with surgery or radiation in patients with locally advanced disease only or in those with biochemical relapse after radical treatment for localised disease. The epic work by Huggins and Hodges will remain a cornerstone in the annals of medical literature because it initiated the use of endocrine therapy in the management of disseminated prostate cancer and showed that the course of neoplastic disease could be changed by rational external intervention. One can state with certainty that there are few articles in science, which have had, or will have, such a lasting impact.

Role of Testosterone Replacement Therapy on Plasma Ghrelin Level before and after Orchiectomy in Male Albino Rats

The aim of the present study is to investigate whether testosterone replacement therapy play a role on plasma ghrelin level before and after orchiectomy in male albino rats. Four groups of animals were studied, control group, control group received testosterone propionate (T.P) 300 µg/Kg subcutaneously (s.c) daily for 4 weeks, orchiectomized group and lastly orchiectomized group receiving T.P by the same regimen as group two. Blood samples were taken at the end of the experimental period for carrying out the hormonal investigations; also body weight was measured from all studied animals.The results of this work showed that subcutaneous administration of T.P to sham operated and orchiectomy rats produces significant decrease in FSH and LH, however it produces significant increase in total testosterone, free testosterone, ghrelin, insulin-like growth factor-I (IGF-I) and total body weight when these results compared to group one and three respectively. Conclusions:We can conclude that plasma ghrelin level significantly increase after testosterone supplementation in both sham operated and orchiectomy rats, also there are +ve correlation between ghrelin level and testosterone level (both total and free), IGF-1 and body weight & negative correlation between ghrelin and FSH & LH.

Morphological and Morphometric Analysis of the Adrenal Cortex of Androgenized Female Rats

Aim: We evaluated the thickness of the adrenal cortex zones of female rats androgenized to mimic polycystic ovary syndrome. Methods: Forty-four female virgin Wistar-Hannover rats were divided into two groups: controls (n = 17) and animals which received testosterone propionate on the 2nd day of life (n = 27). At 90 days of life, after confirmation of persistent estrus, the animals were sacrificed, and the adrenal cortex zones were evaluated. Student’s t test and Levene’s test were used in the statistical analysis (p < 0.05 considered significant). Results: The adrenal glands of the androgenized rats were more voluminous and had a more intensely vascularized zona reticularis than the control animals. The mean thicknesses of zona glomerulosa and zona reticularis in the androgenized rats were 58.4 and 730.7 µm, respectively, significantly thicker than the values in the control group (45.0 and 328.3 µm, respectively). Conclusion: Zona reticularis and zona glomerulosa of the androgenized female rats were significantly thicker than those of the control animals.

Neurosteroids regulate mouse aggression induced by anabolic androgenic steroids

Anabolic androgenic steroid abuse triggers impulsive aggression, anxiety, and depression, which suggests a dysfunction of GABAergic neurotransmission. Socially isolated female mice that have received testosterone propionate (1.45 micromol/kg) treatment for 3 weeks during social isolation express aggression, neurosteroid downregulation, and changes in the cortical mRNA expression of several gamma-aminobutyric acid type A receptor subunits (alpha1, alpha2, gamma2 are decreased by 30-40%, and alpha4 and alpha5 are increased by 50%). Administration of allopregnanolone or the potent selective brain steroidogenic stimulant S-norfluoxetine, in doses (1.8-3.6 micromol/kg) that fail to inhibit 5-hydroxytryptamine reuptake, normalizes olfactory bulb neurosteroid level downregulation and abolishes aggression. This work underscores the role of neurosteroids in the regulation of aggression elicited by testosterone propionate in socially isolated female mice.

Could neonatal testosterone replacement prevent alterations induced by prenatal stress in male rats?

The present study was designed to examine whether testosterone replacement is able to prevent some effects of maternal restraint stress — during the period of brain sexual differentiation — on endocrine system and sexual behavior in male rat descendants. Pregnant rats were exposed to restraint stress for 1 h/day from gestational days 18 to 22. At birth, some male pups from these stressed rats received testosterone propionate. The neonatal testosterone replacement was able to prevent the reduction in anogenital distance at 22 days of age observed in pups from stressed pregnant rats as well as prevents the decrease in testosterone levels during the adulthood of these animals. Testosterone replacement in these males also presented an improvement in sexual performance. In this way, testosterone replacement probably through increasing neonatal level of this hormone was able to prevent the later alterations caused by the prenatal stress during the period of brain sexual differentiation.

Experimental hyperprolactinemia in a rat model: alteration in centrally mediated neuroerectile mechanisms.

The purpose of this study was to induce hyperprolactinemia in adult male rats and determine its effect on the central and peripheral mediated neurogenic as well as myogenic mechanisms of erectile function/dysfunction in a rat model. The use of penile reflexes in awake animals was used to test the effect of both central and peripheral mechanisms. Electrical stimulation of the cavernous nervous was used to test peripheral neural function and intracorporal injection of papaverine was used to test the intactness of the corporal smooth muscles. These mechanisms were further explored by administration of testosterone. Eighteen Fisher-344 200-250 g rats aged 10 weeks were used in this study. Group 1 (n = 6) hyperprolactinemia was induced with subcutaneous (SQ) injection of 5 mg rat prolactin (NIDDK-r-PRL-B-7, biopotency 25 IU/mg) in two divided doses daily for 1 week. Testosterone propionate 100 mg/kg dissolved in sesame oil was given intramuscularly on day 1 (weekly dose). Group 2 (n = 6) control animals received SQ injection of vehicle twice daily and sesame oil I/M on day 1. Group 3 (n = 6) received testosterone propionate. Penile reflexes (erections, cups, flips and clusters) were assessed prior to induction (x 3) of and following one-week state of hyperprolactinemia (day 5, 6 and 7). All animals were trained three times before recording the penile reflexes. The penile reflexes being averaged to give a single composite score for each animal. All animals underwent dissections that isolated the cavernosal bodies and cavernosal nerves. Cavernous nerves were activated and intracorporal pressures were recorded at increasing current magnitude (range 0.5-10 mA). Following that corporal smooth muscle reactivity was determined by increasing injection of papaverine (100-3000 microg). Concentration response curves (CRCs) were then generated by plotting percent change (fractional change to make standardized comparison) to increasing neurostimulation or papaverine concentrations at half-log increments. Serum prolactin was determined by rPRL radioimmunoassay Kit-Amersham while serum testosterone was determined Testosterone ELISA Kit-Neogen. Penile reflexes were normal in all groups at the start of experiment but after 1 week of hyperprolactinemia, reflexes were totally abolished in hyperprolactinemia rats (Group 1) and unchanged in Groups 2 and 3. Response to cavernous nerve activation and resulting rise in intracorporal pressure to increasing current (range 0.5-10 mA) were statistically non-significant in any groups. Similarly the intracorporal pressure response to pharmacologic erection induced by papaverine (100-3000 microg) were also non-statistically significant in any groups. Serum prolactin level in all rats receiving prolactin were > 500 ng/ml and the rat group receiving testosterone, serum level were > 20 x higher than the control rat. This approach allowed more clear separation of central and peripheral mechanism of erection. This study shows a central neurological effect of hyperprolactinemia on erectile function. Hypogonadism does not seem to contribute to the impaired penile reflexes as documented by replacement of testosterone did not recover the centrally mediated penile reflexes. Lowered serum testosterone is secondary phenomenon. These observations may have important implications for the understanding, the mechanism and treatment of men with hyperprolactinemia as well as future research in this field.

Effect of testosterone propionate treatment on thyrotropin secretion of young and old rats in vitro

The aim of this study was to evaluate the influence of androgens on TSH secretion during aging in Dutch rats. Male young (2 months) and old (16–21 months) rats were castrated (Cx) or sham-operated (C) and received testosterone propionate (TP — 4 mg/Kg B.W., im, 7days) or vehicle. Female adult (3 months) and old (12 and 17 months) intact rats received TP or corn oil in the same dose. The rats were decapitated, trunk blood was collected and anterior pituitaries were dissected out for in vitro incubation. In Cx young male rats, only TSH pituitary content showed lower levels than in their controls. Cx TP-treated rats showed higher serum TSH and in vitro basal and TRH-induced TSH secretion, but TP only partially reversed the decrease in pituitary TSH promoted by castration. The old male rats showed lower basal in vitro TSH secretion and pituitary TSH content. In Cx old male rats, serum and basal in vitro TSH concentrations were higher than those of old controls and TP treatment further increased basal in vitro TSH secretion, as well as, stimulated TRH-induced TSH secretion. Interestingly, TP had no effect on intact young or old male rats. However, in intact old female rats, TP stimulated in vitro TSH secretion but, as observed in the intact male, TP had no effect on adult female rats. These results suggest a stimulatory role of testosterone on TSH secretion of young and old male rats. Thereafter, it seems that the testes of old rats secrete some testicular factor that inhibits TSH secretion. However, in male rats with normal testosterone levels TP treatment did not increase further TSH secretion, but in old female rats it had a stimulatory effect.