Testosterone Propionate Treatment Research Articles

EMG Testing throughout behavioral recovery after rat sciatic nerve crush injury results in exuberant motoneuron dendritic hypertrophy.

Peripheral nerve injury (PNI) is the most common type of nerve trauma yet, while injured motoneurons exhibit a robust capacity for regeneration, behavioral recovery is protracted and typically poor. Neurotherapeutic approaches to PNI and repair have primarily focused on the enhancement of axonal regeneration, in terms of rate, axonal sprouting, and reconnection connectivity. Both electrical stimulation (ES) and treatment with androgens [e.g., testosterone propionate (TP)] have been demonstrated to enhance axonal sprouting, regeneration rate and functional recovery following PNI. To date, very little work has been done to examine the effects of ES and/or TP on dendritic morphology and organization within the spinal cord after PNI. The objective of the current study was to examine the impact of treatment with TP and ES, alone or in combination, on the dendritic arbor of spinal motoneurons after target disconnection via sciatic nerve crush injury in the rat. Rats received a crush injury to the sciatic nerve. Following injury, some animals received either (1) no further treatment beyond implantation with empty Silastic capsules, (2) electrical nerve stimulation immediately after injury, (3) implantation with Silastic capsules filled with TP, or (4) electrical nerve stimulation immediately after injury as well as implantation with TP. All of these groups of axotomized animals also received bi-weekly electromyography (EMG) testing. Additional groups of intact untreated animals as well as a group of injured animals who received no further treatment or EMG testing were also included. Eight weeks after injury, motoneurons innervating the anterior tibialis muscle were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. After nerve crush and ES and/or TP treatment, motoneurons innervating the anterior tibialis underwent marked dendritic hypertrophy. Surprisingly, this dendritic hypertrophy occurred in all animals receiving repeated bi-weekly EMG testing, regardless of treatment. When the EMG testing was eliminated, the dendritic arbor extent and distribution after nerve crush in the treated groups did not significantly differ from intact untreated animals. The ability of repeated EMG testing to so dramatically affect central plasticity following a peripheral nerve injury was unexpected. It was also unexpected that gonadal steroid hormones and/or ES, two neurotherapeutic approaches with demonstrated molecular/behavioral changes consistent with peripheral improvements in axonal repair and target reconnection, do not appear to impact central plasticity in a similar manner. The significance of peripheral EMG testing and resulting central plasticity reorganization remains to be determined.

Treatment of androgenetic alopecia by exosomes secreted from hair papilla cells and the intervention effect of LTF.

Androgenetic alopecia (AGA) is the most common cause of chronic progressive hair loss in men, and AGA has a severe negative impact on the quality of life and physical and mental health of patients. Four female C57BL/6 mice were isolated from DP cells in culture (≤4 generations) after stimulation of DPC proliferation by herbal concentrations obtained by the CCK-8 method, and exosomes were isolated by differential centrifugation at low temperature. Testosterone propionate and topical hair removal treatments were used together to establish the C57BL/6 mouse AGA model, which was treated with LTF, 5% minoxidil, and LTF-DPC-EXO, respectively. ELISA was used to detect serum hormone levels, in vivo tracing was used to observe dynamic changes in exosomes, H&E staining showed changes in mouse hair follicle tissue, and (q) RT-PCR and WB were used to detect dorsal skin VEGF, AKT1, and CASP3 expression in dorsal skin tissues. Hair regeneration was significant in the LTF group, minoxidil group, and LTF-DPC-EXO group mice, and the hair growth was only seen in the local skin in the model group. The hormone T in all treatment groups was lower than that in the model group, and e2 was higher than that in the model group. (q) RT-PCR and western blot showed that VEGF and AKT1 expressions were upregulated and Caspase3 expression was downregulated in the skin sections of mice in the treatment groups. DPC-EXO obtained through LTF may activate AKT1 and VEGF in the PI3K/AKT signaling pathway to inhibit CASP3, thereby protecting DPC to restore the hair growth.

Testosterone propionate and Swarna Bhasma treatment modulated D-galactose induced reproductive alterations in male Wistar rats: An experimental study.

The male reproductive system undergoes several adverse age-related changes like decreased hormone synthesis, sperm count, and testicular alteration that can impact on fertility. The study aims to investigate the effects of testosterone propionate (TP), and ayurvedic formulation Swarna Bhasma (SB) on D-galactose (D-gal) induced reproductive aging in male Wistar rats. 60 male Wistar rats were divided into 10 groups of 6 animals. Reproductive aging was induced by D-gal (150 mg/kg Bwt) exposure for 60 days. The rats were then treated by post and combination treatment with TP (2 mg/kg Bwt) and SB (6.75 mg/kg Bwt). Then sperm parameters, reproductive hormones, inflammatory markers, testicular antioxidant enzymes, steroidogenic enzymes, and histological manifestation of testis were evaluated. Exposure of D-gal caused significant (p 0.001) decrease in serum testosterone (T), testicular steroidogenic, and antioxidant enzymes. Administration of TP increased the serum T level, testicular antioxidant enzymes, and spermatogenic profile at a significant level of (p 0.001) compared to D-gal. Further, the SB treatment significantly (p 0.001) elevated the serum T level, sperm count, testicular antioxidant enzymes, steroidogenic enzymes, when compared to D-gal. Both the treatment of TP and SB treatments recovered the reproductive impairments caused by D-gal. However, exogenous T supplementation via TP administration is associated with various side effects during long-term use. SB is an Ayurvedic formulation having a long history of usage in India. The current findings suggest that the SB may be used as a good alternative for potentiating reproductive function in aging males.

Testosterone Propionate Promotes Proliferation and Viability of Bone Marrow Mesenchymal Stem Cells while Preserving Their Characteristics and Inducing Their Anti-Cancer Efficacy

Various studies have reported the effects of testosterone on different cell types, yet bone marrow-derived mesenchymal stem cells’ cellular responses to testosterone remain unknown. To investigate the effects of testosterone propionate, an oil-soluble short-acting form of testosterone, on human bone marrow-derived mesenchymal stem cells’ proliferation and viability after 24 hours of incubation. We also investigated the impact of testosterone propionate on bone marrow-derived mesenchymal stem cell’s polarization and cytotoxicity on K562 leukemia cell line. In vitro study. We expanded commercially available bone marrow derived mesenchymal stem cells in vitro and treated them with testosterone propionate at concentrations ranging from 10-6-10-10 M for 24 hours. Ideal concentration was determined by evaluating cellular viability and proliferation with Annexin V/Propidium Iodide assay and carboxyfluorescein succinimidyl ester staining. The characteristic features of bone marrow-derived mesenchymal stem cells were evaluated by immunophenotyping and investigating their differentiation capacities. Bone marrow-derived mesenchymal stem cells’ cytotoxic properties upon testosterone propionate treatment were determined by co-culturing the cells with K562 cells and with confocal imaging investigating polarization. Testosterone propionate promoted proliferation and maintained the viability of bone marrow-derived mesenchymal stem at 10-8 M concentration. Further evaluations were conducted with the determined dose. The results showed that, apart from promoting mesenchymal stem cells’ polarization and increasing their cytotoxicity on K562 cells, testosterone propionate did not alter differentiation capacities of bone marrow-derived mesenchymal stem cells and certain cell surface markers, but led to a significant increase in HLA-DR expression. The findings reveal that testosterone propionate promotes the proliferation and survival of bone marrow-derived mesenchymal stem cells in a dose-dependent manner without hampering their differentiation capacities, induces their polarization to the pro-inflammatory phenotype, and increases their cytotoxicity on the K562 cell line.

SIRT3 affects mitochondrial metabolic reprogramming via the AMPK–PGC‐1α axis in the development of benign prostatic hyperplasia

Sirtuin 3 (SIRT3) has been reported to share an association with mitochondrial metabolic reprogramming. However, the molecular mechanism underlying is not well understood, especially in benign prostatic hyperplasia (BPH). Therefore, the purpose of this study was to research whether SIRT3 can affect the progression of BPH via the regulation of mitochondrial metabolic reprogramming. Following the development of a rat model of BPH using testosterone propionate (TP), we extracted prostate tissues from sham-operated and BPH rats. Subsequently, bioinformatics prediction was used to screen the genes differentially expressed in BPH. To verify the role played by SIRT3 in BPH, we injected AAV9-SIRT3 into rats, followed by TP treatment. Prostate epithelial cells (PEC) were treated with TP to assess the mitochondrial morphology, mitochondrial membrane potential, and expression of enzymes related to the oxidative phosphorylation pathway after SIRT3 expression alteration. Finally, we examined the expression of AMPK-PGC-1α pathway in tissues and cells. SIRT3 was reduced in the prostate tissues of BPH rats. After overexpression of SIRT3, mitochondrial morphology was more stable in prostate tissues of BPH rats and in TP-treated PEC, with significant increases in mitochondrial membrane potential and in the expression of oxidative phosphorylation-related enzymes in the cytoplasm. Moreover, SIRT3 significantly activated the AMPK-PGC-1α signaling pathway, which maintained the stability of mitochondrial membrane potential as well as mitochondrial structure, thus alleviating the symptoms of BPH. SIRT3 maintained the stability of mitochondrial membrane potential as well as mitochondrial structure by activating the AMPK-PGC-1α pathway, thereby alleviating the symptoms of BPH.

Dihydroartemisinin attenuates benign prostatic hyperplasia in rats by inhibiting prostatic epithelial cell proliferation.

BackgroundBenign prostatic hyperplasia (BPH) is a common urological condition in aging men. While dihydroartemisinin (DHA) exhibits a wide range of pharmacological activities, to date, there have been no studies examining the effects of DHA on BPH.MethodsAn in vivo BPH model was constructed in rats via daily subcutaneous injection of testosterone propionate (TP) for 28 consecutive days. Rats were randomly distributed into four groups and treated as follows: (I) control; (II) TP treatment; (III) TP and finasteride treatment (positive control); and (IV) TP and DHA treatment. At the end of the experiment, rats were sacrificed and the prostate weight, prostate index, thickness of the epithelium, collagen deposition, serum dihydrotestosterone (DHT) levels, 5α-reductase 2 (5AR-2) expression, and proliferating cell nuclear antigen (PCNA) levels in the prostate were examined. Normal human prostatic epithelial RWPE-1 cells were used in in vitro experiments to further investigate the anti-proliferative effects of DHA.ResultsTP increased the prostate weight and prostate index in rats, and this effect was reduced with DHA treatment. In addition, DHA attenuated the morphological changes and collagen deposition in the prostate tissue induced by TP. Furthermore, DHA reduced the expression of PCNA, serum DHT, and prostatic 5AR-2 in rats with TP-induced BPH. In vitro analysis revealed that DHA significantly inhibited the proliferation of TP-treated RWPE-1 cells.ConclusionsDHA significantly inhibited the development of BPH by suppressing serum DHT levels, prostatic 5AR-2 expression, and the proliferation of benign prostatic epithelial cells. Thus, DHA is a novel medicinal agent with potential therapeutic efficacy in the treatment of patients with BPH.

Influence of circulating testosterone concentration on sperm cryoresistance: The ibex as an experimental model

Recent studies have noted that the circulating testosterone concentration may affect the ability of spermatozoa to survive cryopreservation. However, few attempts to confirm such a relationship have been made. Wild ruminant species have very marked seasonal changes in their reproductive function and strong annual changes in their plasma testosterone concentration. The present work examines the influence of induced changes in testosterone secretion on sperm variables following conventional slow freezing and ultra-rapid freezing, using the Iberian ibex as an experimental model. In a first experiment, testosterone levels were reduced in the middle of the rutting season (December) using the antiandrogen cyproterone acetate (CA). In a second experiment, testosterone levels were increased at the end of the rutting season (January) via the use of the androgen testosterone propionate (TP). During December, the testosterone concentration was found to be higher in the blood and seminal plasma of untreated males than in those of CA-treated males (p<0.001 and p<0.05, respectively). Compared with controls, the TP-treated animals had higher blood plasma testosterone concentrations but lower seminal plasma testosterone concentrations during January (p<0.01 and p<0.001, respectively). The seminal vesicles of the TP-treated males were larger than those of untreated males (p<0.05). When CA was administered, sperm viability improved compared with controls (p<0.05), irrespective of the freezing protocol followed. For the ultra-rapid freezing procedure, the cryoresistance ratio for motility decreased when TP was administered (p<0.05). The values for fresh sperm morphometric variables decreased during the 50days after the end of CA treatment (p<0.001) and increased over the same time after the end of TP treatment (p<0.001). The circulating testosterone concentration appears to influence sperm cryoresistance. This may explain the seasonal changes seen in sperm freezability in some species, independent of fresh sperm quality.

Effects of combined ethanol extract of Funtumia africana and Abutilon mauritianum leaves on prostate biomarkers and serum mineral levels in prostatic hyperplasia induced male rats

Introduction: Benign prostatic hyperplasia (BPH) is a prostate disorder in ageing males that negatively affects the quality of life and requires multidimensional approaches to ameliorate its adverse health effects. Objectives: This study evaluated the effects of combined ethanol extract of Funtumia africana and Abutilon mauritianum leaves on the prostate biomarkers, serum mineral levels and prostate histomorphology of BPH induced rats. Materials and Methods: Thirty-six male Wistar albino rats randomly distributed into 5 groups containing 6 rats each was used for this study. Group 1 served as the normal control rats without BPH induction while groups 2–5 were BPH induced rats that served as BPH control (untreated), finasteride control, and BPH induced treated with 200 and 600 mg/kg/d of the combined ethanol extract of F. africana and A. mauritianum leaves respectively. BPH was induced in the rats by subcutaneous injection of 5 mg/kg/d of testosterone propionate injection and treatment followed 1h after the induction for 28 consecutive days. All the biochemical analyses and prostate histological examinations were carried out using standard methods. Results: BPH induction significantly elevated serum prostatic acid phosphatase activities and serum prostate-specific antigen (PSA) concentrations in the BPH control rats relative to the normal control. The BPH induction caused significant (P&lt;0.05) reductions in the serum levels of calcium and selenium levels and significantly increased the serum inorganic phosphate concentration in the BPH control when compared with the normal control. Treatment with the combined extract significantly (P&lt;0.05) increased the serum zinc, calcium, copper, iron and inorganic phosphate and significantly reduced serum selenium level when compared with the BPH control. The combined extract further significant (P&lt;0.0) reduced the serum prostatic acid phosphatase activities and PSA level relative to the BPH control. The BPH control showed severe prostate histomorphological alterations consistent with BPH which were largely reduced to mild alterations in combined extract-treated BPH induced rats. Conclusion: This study revealed that the combined ethanol extract of F. africana and A. mauritianum leaves positively regulate the serum mineral levels, serum prostatic acid phosphatase activities, PSA levels and improves prostate histomorphology BPH induced rats.

D-Chiro-Inositol Treatment Affects Oocyte and Embryo Quality and Improves Glucose Intolerance in Both Aged Mice and Mouse Models of Polycystic Ovarian Syndrome.

Polycystic ovarian syndrome (PCOS) is the main cause of female infertility. It is a multifactorial disorder with varying clinical manifestations including metabolic/endocrine abnormalities, hyperandrogenism, and ovarian cysts, among other conditions. D-Chiro-inositol (DCI) is the main treatment available for PCOS in humans. To address some of the mechanisms of this complex disorder and its treatment, this study examines the effect of DCI on reproduction during the development of different PCOS-associated phenotypes in aged females and two mouse models of PCOS. Aged females (8 months old) were treated or not (control) with DCI for 2 months. PCOS models were generated by treatment with dihydrotestosterone (DHT) on Days 16, 17, and 18 of gestation, or by testosterone propionate (TP) treatment on the first day of life. At two months of age, PCOS mice were treated with DCI for 2 months and their reproductive parameters analyzed. No effects of DCI treatment were produced on body weight or ovary/body weight ratio. However, treatment reduced the number of follicles with an atretic cyst-like appearance and improved embryo development in the PCOS models, and also increased implantation rates in both aged and PCOS mice. DCI modified the expression of genes related to oocyte quality, oxidative stress, and luteal sufficiency in cumulus-oocyte complexes (COCs) obtained from the aged and PCOS models. Further, the phosphorylation of AKT, a main metabolic sensor activated by insulin in the liver, was enhanced only in the DHT group, which was the only PCOS model showing glucose intolerance and AKT dephosphorylation. The effect of DCI in the TP model seemed mediated by its influence on oxidative stress and follicle insufficiency. Our results indicate that DCI works in preclinical models of PCOS and offer insight into its mechanism of action when used to treat this infertility-associated syndrome.

Influence of testosterone administration at the end of the breeding season on sperm cryoresistance in rams (Ovis aries) and bucks (Capra hircus)

This study examines the influence of administering testosterone at the end of the mating season, on the responses (morphometric and functional) of ram and buck sperm to freezing-thawing. Five rams were administered 25 mg testosterone propionate (TP) subcutaneously in 2 mL of olive oil twice per week (Monday and Thursday) from October 1 to 31; 5 bucks received exactly the same treatment but from November 1 to 30. Control groups were administered 2 mL of olive oil without TP twice per week over the same period. In the rams, no significant differences were seen in plasma testosterone between the treated and control groups during treatment (0.8 ± 0.2 ng/mL vs 1.5 ± 0.5 ng/mL; P > 0.05). Significant differences were seen in this respect, however, in the bucks (4.3 ± 0.8 ng/mL and 6.9 ± 0.9 ng/mL; P < 0.05). In the rams, TP treatment increased (P < 0.05) the straight-line velocity (VSL), linearity (LIN), straightness (STR) and wobble (WOB) values in fresh sperm samples. Similarly, in the frozen-thawed samples, TP treatment increased the VSL, average path velocity (VAP), LIN and WOB values (P < 0.05) compared with controls. In the bucks, treatment with TP had no effect on any measured variable in fresh sperm; frozen-thawed sperm, however, returned greater VSL, LIN, STR, and WOB values (P < 0.05) than did controls. In the rams, treatment with TP led to a reduction in all fresh sperm head morphometric variables (P < 0.05). Freezing-thawing further reduced (P < 0.05) all morphometric variables in both the control and treated groups. In the bucks, treatment with TP increased (P < 0.05) the length, area, and perimeter of fresh sperm cells, unlike that seen in ram sperm. Compared with fresh sperm, freezing-thawing led to reduced (P < 0.05) morphometric variables in both the control and treated bucks, except for the sperm head width, which in the controls remained unchanged. In conclusion, TP treatment at the end of the mating season affected fresh sperm quality, in both Spanish Merino rams and Murciano-Granadina bucks, in a species-specific manner, but improved the sperm kinetic variables after freezing-thawing in both species, apparently improving sperm cryoresistance. Treatment with TP affects the dimensions of the sperm head in a species-specific manner.

Effects of testosterone on circadian rhythmicity in old mice.

Serum testosterone concentration decreases with age in humans and rodents. Accordingly, old male mice show changes in locomotor activity rhythms: a lengthened free-running period and decreased activity levels among others. To investigate whether testosterone replacement improves the age-related decline in circadian rhythmicity, we examined the effects of testosterone on the circadian rhythms of wheel running activity in old male mice. Intact male C57BL/6J mice (18-22months old) were subcutaneously implanted with silicone tubes packed with testosterone propionate (TP) or cholesterol. TP treatment significantly decreased the daily wheel running revolutions in a normal light/dark (LD) cycle and in constant darkness (DD), but did not affect the free-running period. The same experiment performed on young male gonadectomized mice (3-5months old) demonstrated that TP treatment significantly increased activity levels in both LD and DD. These results suggest that testosterone replacement exacerbates the age-related decline in circadian rhythmicity.

Effects of alcohol on benign prostate hyperplasia induced by testosterone propionate in mice

To study the effects of alcohol administration on benign prostate hyperplasia(BPH) and the reproductive toxicity during development of benign prostate hyperplasia. Seventy adult male Kunming mice were randomly divided into seven groups:control (group CON), negative control (group NC, injected subcutaneously with soybean oil, 25 mg/(kg·d), intragastric administration of distilled water, 7.5 ml/(kg·d)), alcohol for 7 and 21 days (group AL7 and AL21, intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)), testosterone propionate for 7 and 21 days (group TP7 and TP21, injected subcutaneously with testosterone propionate, 25 mg/(kg·d)), testosterone propionate+alcohol for 7 days (group TP+AL7, injected subcutaneously with testosterone propionate, 25 mg/(kg·d), and intragastric administration with wine of 50% alcohol, 7.5 ml/(kg·d)),10 mice in each groups. Twenty-four hours after the last administration, mice were sacrificed. The indexes of prostate and testis and the parameters of sperm were determined in mice. The levels of free radicals, antioxidation and histopathological changes in testis and prostate were determined. Compared with the control, TP7d group, AL7 and AL21d groups, the prostate coefficient of TP + AL7d group was increased significantly and the quantity and quality of sperm were decreased significantly (P<0.05), the content of MDA in prostate and testis was increased significantly, meanwhile the activities of SOD and GPx were decreased significantly (P< 0.05). Compared with TP21d group, the prostate coefficient of TP + AL7d group had no significant difference (P>0.05). The typical BPH state could be induced after 7-day treatment of testosterone propionate and alcohol. The testicular and sperm were damaged which enhanced the oxidative stress in reproductive system. The results indicated that alcohol could significantly promote the prostate hyperplasia induced by testosterone propionate in mice.

Haloperidol ameliorates androgen-induced behavioral deficits in developing male rats.

The purpose of present study was to infer the potential effects of testosterone increase in some male-based childhood-onset neuropsychiatric disorders, such as Tourette syndrome. Thus, the influence of early postnatal androgen exposure upon the neurobehaviors and its possible neural basis were investigated in the study. Male pup rats received consecutive 14-day testosterone propionate (TP) subcutaneous injection from postnatal day (PND) 7. The TP treatment produced the hyperactive motor behavior and grooming behavior as well as the increased levels of dopamine, tyrosine hydroxylase and dopamine transporter in the mesodopaminergic system and the elevated levels of serotonin in the nucleus accumbens, without affecting the levels of glutamate, γ-aminobutyric acid, norepinephrine and histamine in the caudate putamen and nucleus accumbens of PND21 and PND49 rats. Dopamine D2 receptor antagonist haloperidol was administered to the early postnatal TP-exposed PND21 and PND49 male rats 30 min prior to open field test. Haloperidol significantly ameliorated the motor behavioral and grooming behavioral defects induced by early postnatal TP exposure. The results demonstrated that early postnatal androgen exposure significantly disturbed the brain activity of developing male rats via enhancing the mesodopaminergic activity. It was suggested that abnormal increments of testosterone levels during the early postnatal development might be a potential risk factor for the incidence of some male-based childhood-onset neuropsychiatric disorders by affecting the mesodopaminergic system.

Corni Fructus attenuates testosterone-induced benign prostatic hyperplasia by suppressing 5α-reductase and androgen receptor expression in rats.

BACKGROUND/OBJECTIVESBenign prostatic hypertrophy (BPH) is a major cause of abnormal overgrowth of the prostate mainly in the elderly. Corni Fructus has been reported to be effective in the prevention and treatment of various diseases because of its strong antioxidant effect, but its efficacy against BPH is not yet known. This study was designed to evaluate the therapeutic efficacy of Corni Fructus water extract (CF) in testosterone-induced BPH rats.MATERIALS/METHODSTo induce BPH, rats were intraperitoneal injected with testosterone propionate (TP). Rats in the treatment group were orally administered with CF with TP injection, and finasteride, which is a selective inhibitor of 5α-reductase type 2, was used as a positive control.RESULTSOur results showed that the increased prostate weight and histopathological changes in BPH model rats were suppressed by CF treatment. CF, similar to the finasteride-treated group, decreased the levels of testosterone and dihydrotestosterone by TP treatment in the serum, and it also reduced 5α-reductase expression and concentration in prostate tissue and serum, respectively. In addition, CF significantly blocked the expression of the androgen receptor (AR), AR co-activators, and proliferating cell nuclear antigen in BPH rats, and this blocking was associated with a decrease in prostate-specific antigen levels in serum and prostate tissue.CONCLUSIONSThese results suggest that CF may weaken the BPH status through the inactivation of at least 5α-reductase and AR activity and may be useful for the clinical treatment of BPH.

Psychosis in Kallmann Syndrome: a case illustration based on possible genetic liability

Kallmann Syndrome (KS) is an uncommon disorder caused by a deficient production or secretion of gonadotropin-releasing hormone (GnRH) and manifests with an absence of spontaneous puberty and impaired sense of smell. Multiple inheritance patterns have been recognized in the etiology. KS and psychosis have occasionally been con-sidered to originate in similar predisposing genetic profile. Defective KAL-X gene which had previously been attributed in the etiopathogenesis of schizophrenia was asserted to lead to an impairment in the migration of GnRH neurons and olfactory deficits in various severity and disruption in sexual developmental, consequently. Our case is a 19-year-old male previously diagnosed with KS at his 13, who has been under the monthly intramuscular treat-ment of testosterone propionate and testosterone phenylpropionate at the dose of 250 mg. He was admitted to our clinic with auditory and visual hallucinations that started two years ago. Persecutory delusions, social isolation, and suicidal thoughts also existed. We diagnosed him schizophrenia with comorbid KS following the hospitalization and a detailed psychiatric examination. Olanzapine was initiated as 5 mg/day and potentiated to 15 mg/day. His delu-sions, hallucinations and suicidal thoughts had improved with the treatment. In this illustration, we purposed to discuss probable common etiopathogenesis underlying this comorbidity.

The clinical research of hypospadias with small glans

Objective To explore treatment scheme and surgery for hypospadias with small glans. Methods Between January 2014 and January 2017, 40 cases of hypospadias with small glans were enrolled in the study including 13 cases with penile hypospadias and 27 cases with penoscrotal hypospadias. The boys′s average age was 1.5 years, aged from 1 to 5 years old. The boys whoes glans width less than 10 mm received the treatment of topical testosterone propionate smeared on penis once a day for 1 or 2 months. The patients received operation when their glans width reached 10 mm to 14 mm. Among of 27 cases of severe penile recurvation patients, 17 cases received staging operation, one-stage was correction of penile recurvation and two-stage was Tubularized incised plate with pull-through procedure, 10 cases received adopted modified Duplay combined with Duckett operation, then overturn split-skin graft for incision in the urethra located in glans penis. Among of 13 cases with mild and moderate recurvation, after penile correction, 3 cases received Tubularized incised plate urethroplasty and 10 cases received Onlay island flap urethroplasty. All of the patients received modified plastic surgery for glans. Results All of patients were followed-up, from 3 months to 3 years. The surgical success rate was 70%(28/40).12 cases got operative complications, including urinary fistula 6 cases and glans dehiscence 1 case, who were cured by reoperation, external orifice stricture 1 case and urethral stricture 4 cases who were healed by Urethra dilatation. All patients acquired good appearance glans and satisfied void stream. Conclusions Topical use testosterone propionate for hypospadias with small glans helps the growth of penis. Individualized diagnosis and treatment plan should be made for the particular case of hypospadias with small glans. The modified plastic surgery of glans is suitable for hypospadias with small glans, which could improve surgery success rate and reduce the postoperative complication. Key words: Hypospadias; Small glans; Urethroplasty; Child

RETRACTED: Testosterone promotes anxiolytic-like behavior in gonadectomized male rats via blockade of the 5-HT1A receptors

This study was designed to examine an anxiety-like behavior in the adult gonadectomized (GDX) male rats subjected to testosterone propionate (TP) treatment alone or in combination with 8-OH-DPAT, a 5-HT1A receptor agonist, or with NAN-190, 5-HT1A receptor antagonist. Two weeks after gonadectomy, GDX rats were subjected by treatments with the solvent, TP (0.5mg/kg, s.c.), 8-OH-DPAT (0.05mg/kg, s.c.), NAN-190 (0.1mg/kg, i.p.), TP in combination with 8-OH-DPAT or NAN-190 during 14days. Anxiety behavior was assessed in the elevated plus maze (EPM) and the open field test (OFT). 8-OH-DPAT treatment failed to modify the anxiety-like behavior of GDX rats in the EPM as compared to the GDX rats given with oil solvent. NAN-190 injected alone or in combination with TP to GDX rats resulted in a significant anxiolytic-like effect as compared to the GDX given with oil solvent or TP application. Our data indicate that the combination of NAN-190 and TP is more effective than TP alone in GDX rats inducing a more profound anxiolytic-like effect in the EPM. Thus, the results of this study suggest that effects of 5-HT1A receptor agonist/antagonist can modify anxiety level in opposite direction in male rats after gonadectomy.

Polycystic ovary syndrome induced by exposure to testosterone propionate and effects of sympathectomy on the persistence of the syndrome

Polycystic ovary syndrome is a complex disorder affecting 6 to 10% of women of reproductive age. In recent years, the cause of the syndrome has been associated with increased androgen serum levels, as well as sympathetic nervous system hyperactivity. The present study analyzed the effects at birth of a single testosterone propionate dose in rats, as well as the role of the superior ovarian nerve in polycystic ovary syndrome persistence. Newborn female rats of the CIIZV strain were injected with a single dose of 100 μg testosterone propionate, or corn oil as a vehicle. At 24 days of age, rats were subjected to superior ovarian nerve unilateral or bilateral section. A group of animals was sacrificed on their first vaginal estrus, and a second group was sacrificed at 90 days of age, when they presented an estrus preceded by a proestrus. Testosterone propionate administration at birth blocked ovulation both in adult animals and in animals sacrificed on the first vaginal estrus. Histological analysis of testosterone propionate-treated adult rat ovaries revealed the development of follicular cysts. Ovulation could not be restored by unilateral or bilateral section, and ovaries presented follicular cyst and absence of corpora lutea. Our results suggest that testosterone propionate treatment at birth results in the development of polycystic ovary syndrome, and that this outcome is not due to superior ovarian nerve noradrenergic innervation hyperactivity.

Cardiac hypertrophy and IGF-1 response to testosterone propionate treatment in trained male rats

AbstractObjectiveSeveral studies have suggested that testosterone exerts a growth-promoting effect in the heart. Limited data are available regarding interactions between possible endocrine/paracrine effects in response to exercise training. Therefore, we examined supraphysiological testosterone-induced heart hypertrophy and cardiac insulin-like growth factor (IGF)-1 content in sedentary and exercise-trained rats.DesignMale Wistar rats (n=33) were randomly allocated to groups with a 6-week endurance training with or without testosterone, and sedentary animals with or without testosterone. The hormone (20 mg/250 g body weight was administrated once a week for six weeks. After six weeks the animals were anesthetized, euthanized and the heart was excised and weighed. The left ventricle was separated for biochemical analyses.ResultsTestosterone-treated animals showed significantly higher cardiac IGF-1 content compared to untreated control and trained groups (p=0.01). The administration of supraphysiological testosterone significantly increased the heart weight to body weight ratio (HW/BW, p&lt;0.01). A significant positive correlation was seen between IGF-1 levels and the HW/BW ratio (p=0.002; r=0.50) and between serum total testosterone levels and HW/BW (p=0.000; r=0.79).ConclusionsThe results demonstrate that increased cardiac IGF-1 content in response to higher serum testosterone might be responsible for heart hypertrophy observed in both sedentary and endurance-trained animals.

Influence of testosterone on phase II metabolism and availability of soy isoflavones in male Wistar rats.

Genistein and daidzein are the main isoflavones in soy. Their potential beneficial or adverse effects in males like the prevention of prostate cancer or the impact on reproductive functions are controversially discussed. Major determinants of their bioactivity are the absorption and biotransformation of isoflavones. In this study, we focused on the influence of testosterone on plasma availability and phase II metabolism of isoflavones. Male Wistar rats, receiving an isoflavones rich diet, were randomized into three groups: Two groups were orchiectomized (ORX) at postnatal day (PND) 80 and treated for 11days with testosterone propionate (TP) (ORX TP group) or a vehicle (ORX group) after a 7days lasting hormonal decline. The third group served as control and remained intact. Rats were sacrificed at PND 98. ORX rats had reduced isoflavones plasma levels. Differently regulated mRNA expressions of transporters relevant for transport of phase II metabolites in liver and kidney may be responsible for this reduction, more precisely Slc10a1 and Slc21a1 in kidney as well as Slc22a8 in liver. While main phase II metabolites in intact rats were disulfates and sulfoglucuronides, the amount of sulfate conjugates was significantly diminished by ORX. In accordance with that, mRNA expression of different sulfotransferases was reduced in liver by ORX. The observed effects could be almost restored by TP treatment. In conclusion, testosterone, and likely further androgens, has a huge impact on phase II metabolism and availability of isoflavones by influencing the expression of different sulfotransferases and transporters.