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Bioscience Reports Feb 2020Among patients with intensive care unit-acquired weakness (ICUAW), skeletal muscle strength often decreases significantly. The present study aimed to explore the effects...
Among patients with intensive care unit-acquired weakness (ICUAW), skeletal muscle strength often decreases significantly. The present study aimed to explore the effects of testosterone propotionate on skeletal muscle using rat model of sepsis. Male SD rats were randomly divided into experimental group, model control group, sham operation group and blank control group. Rats in experimental group were given testosterone propionate two times a week, 10 mg/kg for 3 weeks. Maximal contraction force, fatigue index and cross-sectional area of the extensor digitorum longus (EDL) were measured. Myosin, IGF-1, p-AKT and p-mTOR levels in EDL were detected by Western blot. Histological changes of the testis and prostate were detected by hematoxylin and eosin staining. We found that maximal contraction force and fatigue index of EDL in experimental group were significantly higher than in model control group. Cross-sectional area of fast MHC muscle fiber of EDL in group was significantly higher than in model control group. The levels of myosin, IGF-1, p-AKT and p-mTOR of EDL in experimental group were significantly higher than in model control group. In addition, no testicle atrophy and prostate hyperplasia were detected in experimental group. In conclusion, these results suggest that testosterone propionate can significantly improve skeletal muscle strength, endurance and volume of septic rats, and the mechanism may be related to the activation of IGF-1/AKT pathway. Moreover, testosterone propionate with short duration does not cause testicular atrophy and prostate hyperplasia in septic rats. Therefore, testosterone propionate is a potential treatment for muscle malfunction in ICUAW patients.
Topics: Androgens; Animals; Disease Models, Animal; Insulin-Like Growth Factor I; Male; Muscle Contraction; Muscle Fatigue; Muscle Strength; Muscle Weakness; Muscle, Skeletal; Myosins; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Sepsis; TOR Serine-Threonine Kinases; Testosterone Propionate
PubMed: 31967292
DOI: 10.1042/BSR20193342 -
Frontiers in Physiology 2022Obesity, an important risk factor for cardiovascular disease, promotes vascular oxidative stress. Considering that free testosterone levels remain within the reference...
Obesity, an important risk factor for cardiovascular disease, promotes vascular oxidative stress. Considering that free testosterone levels remain within the reference range, especially in obese young men and that testosterone stimulates reactive oxygen species (ROS) generation, we sought to investigate whether testosterone interferes with obesity-associated oxidative stress and vascular dysfunction in male mice. We hypothesized that testosterone favors ROS accumulation and vascular dysfunction in high fat diet (HFD)-fed obese mice. We also questioned whether testosterone downregulates the nuclear factor E2-related factor 2 (Nrf2), one of the major cellular defense mechanisms against oxidative stimuli. Male C57Bl/6J mice were submitted to orchiectomy or sham-operation. Mice received either a control diet (CD) or HFD for 18 weeks. Vascular function was assessed in thoracic aortic rings and molecular mechanisms by which testosterone contributes to vascular dysfunction were determined. HFD reduced acetylcholine-induced vasodilation and increased vascular ROS generation in sham mice. Castration prevented these effects. Treatment of castrated mice fed either the CD or HFD with testosterone propionate decreased acetylcholine vasodilation. HFD decreased Nrf2 nuclear accumulation, events linked to decreased mRNA expression and activity of Nrf2-regulated enzymes (catalase, heme oxygenase-1, peroxiredoxin, and thioredoxin). These events were prevented in HFD-fed castrated mice. Bardoxolone, a Nrf2 activator, increased nuclear accumulation of Nrf2, decreased ROS generation and improved acetylcholine vasodilation in HFD-fed sham mice. , testosterone increased ROS generation and decreased Nrf2 nuclear accumulation. These effects were prevented in the presence of an androgen receptor antagonist, an inhibitor of gene transcription and an inhibitor of the pro-oxidant enzyme NOX-1. These results indicate that testosterone downregulates Nrf2, leading to oxidative stress and vascular dysfunction in HFD-fed obese young mice.
PubMed: 35350697
DOI: 10.3389/fphys.2022.837603 -
Nutrients Apr 2024Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly...
Benign prostatic hyperplasia (BPH) is the non-malignant enlargement of the prostate, associated with lower urinary tract symptoms (LUTSs). Taraxaci Herba (TH), commonly known as dandelion, has traditionally been utilized in East Asia to treat symptoms related to LUTSs. Based on this traditional use, our study aimed to explore the inhibitory effects of TH on BPH progression using a testosterone propionate-induced rat model. To induce BPH, male Sprague Dawley rats were castrated and injected subcutaneously with testosterone propionate (3 mg/kg/day) for 28 days. Concurrently, TH extract was administered orally at doses of 100 and 300 mg/kg/day throughout the four-week period of testosterone propionate injections. The TH extract significantly reduced both the absolute and relative weights of the prostate, along with histopathological changes in the gland. Moreover, it lowered serum levels of testosterone and dihydrotestosterone and reduced the expression of the androgen receptor in the prostate. Additionally, the TH extract modulated the protein expressions of Bax and Bcl-2, which are key regulators of apoptosis in prostate cells. Collectively, our findings suggest that TH inhibits BPH development partially by modulating androgen signaling and inducing apoptosis within the prostate.
Topics: Male; Animals; Prostatic Hyperplasia; Testosterone Propionate; Rats, Sprague-Dawley; Prostate; Plant Extracts; Rats; Apoptosis; Disease Models, Animal; Testosterone; Receptors, Androgen; Dihydrotestosterone; bcl-2-Associated X Protein; Proto-Oncogene Proteins c-bcl-2
PubMed: 38674879
DOI: 10.3390/nu16081189 -
Biological & Pharmaceutical Bulletin 2018Mast cell and testosterone interactions involved in renal fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Orchiectomized (ORX) and...
Mast cell and testosterone interactions involved in renal fibrosis in rats subjected to unilateral ureteral obstruction (UUO) were investigated. Orchiectomized (ORX) and nonorchiectomized Wistar rats were subjected to UUO, and a nonorchiectomized group was sham-operated (control: SO). Animals from the UUO group were treated with saline or sodium cromoglycate (CG). Some ORX rats from the saline or CG groups also received testosterone propionate replacement (TR). Kidneys and blood were collected 14 d after UUO or SO. Kidney sections were stained with toluidine blue to quantify mast cells, and picrosirius red was used for collagen analysis. Immunohistochemistry for α-smooth muscle actin (α-SMA) and proliferating cell nuclear antigen (PCNA) expression was also performed. Plasma testosterone levels (PTLs) were measured. ORX decreased and TR normalized PTLs. UUO increased mast cell density in the kidney pelvis, but not in the kidney parenchyma. UUO increased mast cell degranulation, and CG or ORX inhibited this effect. TR partially reversed the effect of ORX on mast cell degranulation, and CG partially inhibited that effect of TR. UUO increased the collagen areas of the renal parenchyma, whereas CG or ORX abolished that alteration; TR reversed the effects of ORX, and CG partially inhibited that effect of TR. UUO increased tubulointerstitial α-SMA expression and PCNA-positive cells, and these changes were sensitive to ORX or CG to the same degree, while TR again reversed the effect of ORX. Renal fibrosis after UUO appears to be determined by interactions between testosterone and mast cells.
Topics: Actins; Animals; Cell Degranulation; Collagen; Creatinine; Fibrosis; Glomerular Filtration Rate; Hormone Replacement Therapy; Kidney; Kidney Diseases; Male; Mast Cells; Orchiectomy; Rats, Wistar; Testosterone; Ureteral Obstruction
PubMed: 30068865
DOI: 10.1248/bpb.b17-00829 -
Psychoneuroendocrinology Nov 2020Studies suggest that males outperform females on some spatial tasks. This may be due to the effects of sex steroids on spatial strategy preferences. Past experiments...
Studies suggest that males outperform females on some spatial tasks. This may be due to the effects of sex steroids on spatial strategy preferences. Past experiments with male rats have demonstrated that low doses of testosterone bias them toward a response strategy, whereas high doses of testosterone bias them toward a place strategy. We investigated the effect of different testosterone doses on the ability of male rats to effectively employ these two spatial learning strategies. Furthermore, we quantified concentrations of brain-derived neurotrophic factor (pro-, mature-, and total BDNF) in the prefrontal cortex, hippocampus, and striatum. All rats were bilaterally castrated and assigned to one of three daily injection doses of testosterone propionate (0.125, 0.250, or 0.500 mg/rat) or a control injection of the drug vehicle. Using a plus-maze protocol, we found that a lower testosterone dose (0.125 mg) significantly improved rats' performance on a response task, whereas a higher testosterone dose (0.500 mg) significantly improved rats' performance on a place task. In addition, we found that a low dose of testosterone (0.125 mg) increased total BDNF in the striatum, while a high dose (0.500 mg) increased total BDNF in the hippocampus. Taken altogether, these results suggest that high and low levels of testosterone enhance performance on place and response spatial tasks, respectively, and this effect is associated with changes in BDNF levels within relevant brain regions.
Topics: Animals; Brain; Brain-Derived Neurotrophic Factor; Corpus Striatum; Hippocampus; Male; Maze Learning; Orchiectomy; Prefrontal Cortex; Rats; Rats, Inbred F344; Spatial Learning; Testosterone
PubMed: 32892065
DOI: 10.1016/j.psyneuen.2020.104850 -
Molecules (Basel, Switzerland) Nov 2019The effect of Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a...
The effect of Boriss extract irradiated with 50 kGy gamma rays (HKC) on benign prostatic hyperplasia (BPH) was investigated. Seven-week-old male SD rats received a subcutaneous injection of 20 mg/kg of testosterone propionate (TP) to induce BPH. Then, the testosterone only group received testosterone, the testosterone + finasteride group received testosterone and finasteride (5 mg/kg), the testosterone + HKC group received testosterone and HKC extract (500 mg/kg). Prostate weight and the dihydrotestosterone (DHT) levels in serum or prostate tissue were determined. The mRNA expressions of 5-alpha reductase (AR) in prostate tissue were also measured. Compared to the control group, prostate weight was significantly improved in the TP group and decreased in the HKC and finasteride-treated groups. Furthermore, the mRNA expression of 5-AR in the prostate was significantly reduced in the HKC and finasteride-treated groups. Similarly, the expression levels of α-smooth muscle actin (α-SMA) and cytokeratin, which are associated with prostatic enlargement in the HKC and finasteride groups, were much lower than in the TP group. HKC treatment showed similar efficacy to finasteride treatment on rats with testosterone-induced BPH. HKC may be explored as a potential new drug for BPH treatment.
Topics: Animals; Cholestenone 5 alpha-Reductase; Gamma Rays; Male; Plant Extracts; Prostatic Hyperplasia; Rats; Rats, Sprague-Dawley; Rhodiola; Testosterone
PubMed: 31689885
DOI: 10.3390/molecules24213981 -
Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia.International Neurourology Journal Sep 2021To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of rats.
PURPOSE
To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of rats.
METHODS
BPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65.
RESULTS
Injection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone.
CONCLUSION
Androgen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.
PubMed: 34610715
DOI: 10.5213/inj.2142004.002 -
International Journal of Nanomedicine 2013The current investigation aimed to evaluate the transdermal potential of novel testosterone propionate (TP) ethosomes and liposomes prepared by surfactant modification....
The current investigation aimed to evaluate the transdermal potential of novel testosterone propionate (TP) ethosomes and liposomes prepared by surfactant modification. The effect of hexadecyl trimethyl ammonium bromide and cremophor EL-35 on the particle size and zeta potential of the prepared vesicles was investigated. The entrapment efficiency and stability, as well as in vitro and in vivo skin permeation, were studied with the various techniques, such as differential scanning calorimetry, confocal laser scanning microscopy, transmission electron microscopy, dynamic light scattering, and so on. The results indicated that the ethosomes were defined as spherical, unilamellar structures with low polydispersity (0.100 ± 0.015) and nanometric size (156.5 ± 3.5 nm). The entrapment efficiency of TP in ethosomal and liposomal carriers was 92.7% ± 3.7% and 64.7% ± 2.1%, respectively. The stability profile of the prepared TP ethosomal system assessed for 120 days revealed very low aggregation and very low growth in vesicular size. TP ethosomes also provided an enhanced transdermal flux of 37.85 ± 2.8 μg/cm(2)/hour and a decreased lag time of 0.18 hours across mouse skin. The skin permeation efficiency of the TP ethosomes as further assessed by confocal laser scanning microscopy revealed enhanced permeation of rhodamine red-loaded formulations to the deeper layers of the skin (260 μm) than that of the liposomal formation (120 μm).
Topics: Administration, Cutaneous; Animals; Biological Availability; Cetrimonium; Cetrimonium Compounds; Drug Stability; Ethanol; Liposomes; Male; Mice; Microscopy, Confocal; Particle Size; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility; Surface-Active Agents; Testosterone Propionate
PubMed: 23990718
DOI: 10.2147/IJN.S46748 -
Iranian Journal of Basic Medical... Jan 2023This study was designed to investigate the protective effects of extract on testosterone-induced benign prostatic hyperplasia in rats.
OBJECTIVES
This study was designed to investigate the protective effects of extract on testosterone-induced benign prostatic hyperplasia in rats.
MATERIALS AND METHODS
In this study, 60 adult Sprague Dawley rats were randomly divided into six equal groups, one group served as the normal control, five of the groups were administered subcutaneous testosterone propionate for 28 days to induce benign prostatic hyperplasia, three of the five groups were simultaneously administered three graded doses of extract while one group was administered finasteride as the standard drug and the other left as untreated BPH model group given testosterone propionate only. BPH in the prostate gland was detected through gross appearance, prostate weight, and biochemical and histopathological analyses.
RESULTS
Increased prostate weight, serum prostate-specific antigen (PSA), and epithelial thickness were observed in the untreated testosterone-induced BPH model. Administration of finasteride and extract led to a reduction in prostate weight, prostatic index, serum PSA, serum levels of testosterone, and prostatic epithelial thickness, and increased luminal diameter.
CONCLUSION
Administration of extract suppressed the pathophysiological effects of benign prostatic hyperplasia in rats. Thus, mushroom is a potential pharmacological candidate for the management of BPH in man or dogs.
PubMed: 36594056
DOI: 10.22038/IJBMS.2022.64972.14309 -
Frontiers in Physiology 2021Excessive carotid body responsiveness to O and/or CO/H stimuli contributes to respiratory instability and apneas during sleep. In hypogonadal men, testosterone...
Excessive carotid body responsiveness to O and/or CO/H stimuli contributes to respiratory instability and apneas during sleep. In hypogonadal men, testosterone supplementation may increase the risk of sleep-disordered breathing; however, the site of action is unknown. The present study tested the hypothesis that testosterone supplementation potentiates carotid body responsiveness to hypoxia in adult male rats. Because testosterone levels decline with age, we also determined whether these effects were age-dependent. hybridization determined that androgen receptor mRNA was present in the carotid bodies and caudal nucleus of the solitary tract of adult (69 days old) and aging (193-206 days old) male rats. In urethane-anesthetized rats injected with testosterone propionate (2 mg/kg; i.p.), peak breathing frequency measured during hypoxia (FiO = 0.12) was 11% greater vs. the vehicle treatment group. Interestingly, response intensity following testosterone treatment was positively correlated with animal age. Exposing carotid body preparations from young and aging rats to testosterone (5 nM, free testosterone) 90-120 min prior to testing showed that the carotid sinus nerve firing rate during hypoxia (5% CO + 95% N; 15 min) was augmented in both age groups as compared to vehicle (<0.001% DMSO). Ventilatory measurements performed using whole body plethysmography revealed that testosterone supplementation (2 mg/kg; i.p.) 2 h prior reduced apnea frequency during sleep. We conclude that in healthy rats, age-dependent potentiation of the carotid body's response to hypoxia by acute testosterone supplementation does not favor the occurrence of apneas but rather appears to stabilize breathing during sleep.
PubMed: 35002764
DOI: 10.3389/fphys.2021.781662