Serum Dihydrotestosterone Levels Research Articles

Dihydrotestosterone induces reactive oxygen species accumulation and mitochondrial fission leading to apoptosis of granulosa cells

Dihydrotestosterone (DHT), which has significant androgenic activity，is a major player in follicle development and ovary function in females. However, an excess of androgens may result in increased follicular apoptosis with adverse effects on female fertility. This study aimed to explore the mechanism by which DHT induces apoptosis in human ovarian granulosa cells (GCs). The association between DHT and GC apoptosis was explored by the construction of rat models of polycystic ovary syndrome (PCOS). It was found that serum DHT levels were negatively correlated with thickness of the GC layer in PCOS model rats (R2=0.8342, p＜0.0001), compared with control rats, together with significant increases in cofactors (Fis1: p=0.008; MFF: p=0.044). The GC SVOG cell line was used to clarify the mechanism by which DHT influenced GC apoptosis in in vitro experiments. The results confirmed that apoptosis in SVOG cells was positively associated with the DHT dose. The expression of the autophagy-related proteins LC3A/B (p=0.027) and the proapoptotic protein Bax (p=0.0095) were increased, while that of the anti-apoptotic protein Bcl-2 (p=0.0005) was decreased in the high-dose DHT group. ROS levels were significantly increased (p=0.0237) and the mitochondrial membrane potential ΔΨm was decreased (p=0.0194). Moreover, ultrastructural analysis of the mitochondria indicated significant damage. The results of RT-qPCR and western blotting showed that two fission cofactor-Fis1（p=0.034） and MFF (p=0.039) were significantly increased after treatment with high doses of DHT. Even though the overall expression of Drp1 did not change significantly (p=0.5961), that of activated Phosphor-Drp1(Ser616) was significantly increased (p=0.046), while the expression of Phosphor-Drp1 (Ser637) was markedly reduced (p=0.007) following exposure to high concentrations of DHT. All these effects could be reversed by the Drp1 inhibitor Mdivi-1. These findings indicated the impact of DHT on ROS aggregation and mitochondrial fission, resulting in GC apoptosis. An imbalance in Drp1 phosphorylation may be the key link in DHT-induced excessive mitochondrial fission.

Ixeris polycephala Extract Alleviates Progression of Benign Prostatic Hyperplasia via Modification of Proliferation, Apoptosis, and Inflammation.

Benign prostatic hyperplasia (BPH) is a urogenital disorder that is common in aging men. Ixeris polycephala (IP) is used in traditional medicine and contains pharmacologically active compounds. However, the effect for BPH progression has not been elucidated. We herein examined the protective potential of IP extract on a testosterone-induced model of BPH in rats. To generate the BPH model, daily subcutaneous administration of testosterone was applied for 4 weeks. During this period, the rats were also administered a daily oral gavage of IP (150 mg/kg), finasteride (positive control), or vehicle. Testosterone treatment was associated with a significantly higher prostate-to-body weight ratio, serum dihydrotestosterone (DHT) level, and prostatic gene expression of 5α-reductase compared to untreated controls. Notably, IP plus testosterone co-treatment was associated with decreased epithelial thickness, down-regulation of proliferating cell nuclear antigen (PCNA) and cyclin D1, and upregulation of pro-apoptotic signaling molecules. IP co-treatment also down-regulated pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) and decreased inflammatory cell infiltration compared to the levels seen in the testosterone-induced BPH. IP appears to protect rats against the progression of testosterone-induced BPH by alleviating prostate cell growth and inflammatory responses, and thus may have potential for clinical use against BPH progression.

Ethanol Extracts of Cornus alba Improve Benign Prostatic Hyperplasia by Inhibiting Prostate Cell Proliferation through Modulating 5 Alpha-Reductase/Androgen Receptor Axis-Mediated Signaling.

The aim of this study was to investigate the efficacy of ethanol extracts of Cornus alba (ECA) against benign prostatic hyperplasia (BPH) in vitro and in vivo. The prostate stromal cells (WPMY-1) and epithelial cells (RWPE-1) were used to examine the action mechanism of ECA in BPH in vitro. ECA efficacy was evaluated in vivo using a testosterone propionate (TP)-induced BPH rat model. Treatment with ECA inhibited the proliferation of prostate cells by inducing G1-phase cell cycle arrest through the regulation of positive and negative proteins. Treatment of prostate cells with ECA resulted in alterations in the mitogen-activated protein kinases and protein kinase B signaling pathways. The transcriptional binding activity of the NF-κB motif was suppressed in both ECA-treated prostate cells. In addition, treatment with ECA altered the level of BPH-associated axis markers (5α-reductase, fibroblast growth factor-2, androgen receptor, epidermal growth factor, Bcl-2, and Bax) in both cell lines. Finally, the administration of ECA attenuated the enlargement of prostatic tissues in the TP-induced BPH rat model, accompanied by histology, immunoblot, and serum dihydrotestosterone levels. These results demonstrated that ECA exerted beneficial effects on BPH both in vitro and in vivo and might provide valuable information in the development of preventive or therapeutic agents for improving BPH.

A decrease in serum dihydrotestosterone levels in 9-year-old Vietnamese children from a dioxin exposure area.

Dioxin is an environmental pollutant as well as an endocrine disruptor in humans. Our longitudinal study wants to clarify the relationship between dioxin exposure and endocrine disorders in children living in the Vietnamese dioxin hotspot. Seventeen congeners of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzo-furans (PCDDs/PCDFs) in maternal breast milk and seven serum steroid hormones in children of 43 and 46 mothers and their 9-year-old children from the non-exposure and the hotspot areas were measured, respectively. The steroid metabolic enzyme ratios were calculated based on the hormone level ratio. Most dioxin/furan congeners and toxic equivalents (TEQs) levels were significantly higher in the hotspot than in the non-exposure area, except for 2,4,7,8-TeCDF. The height and weight of girls from the hotspot area were substantially lower and inversely correlated with dioxin congener levels/total TEQs level dioxin. The dihydrotestosterone (DHT) levels in the hotspot were markedly lower than those in non-exposed in both genders. The cortisol concentrations were significantly higher in the hotspot than those from the non-exposure area only in the girls. The DHT/testosterone ratios that exhibited the 5α- or 5β-reductase activity declined by 50% in the hotspot area for both genders. The DHT levels showed strong inverse correlations with almost the PCDDs/PCDFs congeners and total TEQs dioxin in breast milk. This finding suggests that dioxin exposure in maternal breast milk might impact children's endocrine system until 9 years old, especially on the DHT biosynthesis.

Cervi Parvum Cornu complex for men with lower urinary tract symptoms: a multicenter, randomized, double-blind, placebo-controlled trial

BackgroundTo evaluate the efficacy and safety of Cervi Parvum Cornu, Angelicae Gigantis Radix and Glycyrrhizae Radix complex (CAG) in men with moderate lower urinary tract symptoms (LUTS). Materials and methodsFrom November 2020 to January 2022, participants with International Prostate Symptom Score (IPSS) of 12–19 in two centers were recruited and randomize into three groups: a CAG 500 mg/day group (CAG 500), a CAG 1000 mg/day group (CAG 1000), and a placebo group (PG). They were treated for 12 weeks. The primary endpoint was change of IPSS at the end of study from baseline. Secondary end points included change of prostate specific antigen (PSA), testosterone, dihydrotestosterone (DHT), maximum urinary flow rate (Q max), post-void residual volume (PVR), International Index of Erectile Function (IIEF), and drug safety. ResultsA total of 103 patients were able to finish the study according to the study protocol. Total IPSS and sub-scores (residual urine sensation, frequency, weak stream, hesistancy, nocturia, and quality of life) in CAG 500 and CAG 1000 were significantly improved at the 12th week compared to those of the PG. Changes of serum PSA, DHT, and testosterone levels at the 12th week from baseline did not show significant differences among the three groups. Q max and PVR changes did not show significant differences among the three groups either. Total IIEF and sub-scores (erectile function, orgasmic function, sexual desire, intercourse satisfaction) in CAG 1000 were significantly improved at 12th week compared to those in PG. No significant adverse events were found. ConclusionsCAG is well tolerated in patients with moderate LUTS. Treatment with CAG for 12 weeks has a therapeutic effect on moderate LUTS.

Inhibitory Effects of Pueraria mirifica Aqueous Extracts on 5α-reductase and Prostate Histomorphometry in Testosterone-induced Benign Prostatic Hyperplasia Sprague Dawley Rats

Introduction: Benign prostatic hyperplasia (BPH) is the most prevalent prostatic disease in ageing men, characterised by an excessive proliferation of the prostatic epithelial and stromal cells. Despite the extensive choices of pharmaceutical therapies, the current treatments possess side effects, necessitating the search for new alternative options, including herbal substances such as Pueraria mirifica. This tuberous root of P. mirifica is a medicinal plant that contains numerous phytoestrogens, traditionally used for health rejuvenation in aged men and women. This study was carried out to access the inhibitory effect of 5α-reductase of P. mirifica and its histoprotective effect in a rat model of testosterone-induced BPH. Methods: Adult Sprague Dawley (12 weeks) were subcutaneously injected with testosterone propionate (3 mg/kg) daily to induce BPH. Rats (n=6) in all groups (aqueous extract of P. mirifica (APM): 10, 100, and 1000 mg/kg, p.o.; finasteride: 2mg/kg, p.o., BPH model, and sham groups) were treated for 30 days. The determination of serum dihydrotestosterone (DHT) level, prostatic index and prostate structural changes were investigated. Results: APM and finasteride-treated groups showed significantly lesser prostatic weight and prostatic index, serum DHT levels compared to the model group (p<0.05). Furthermore, there was a significantly lower prostate score with improved prostate histomorphology, demonstrating fewer epithelial involutions of glandular tissues and improved stromal and epithelial cells. Conclusion: In conclusion, the aqueous extract of P. mirifica tuberous root mitigates the development of BPH and it can be inferred that aqueous extract of P. mirifica tuberous root may possess the active agents for anti-BPH treatment.

Testosterone or dihydrotestosterone: what should be evaluated in hirsutism?

Dihydrotestosterone is a more potent androgen derived from testosterone and androstenediones, but its measurement has not been routinely recommended in women with hirsutism, and there is limited information in this regard with equivocal findings. This study aimed to evaluate serum dihydrotestosterone level in patients with hirsutism compared to women without hirsutism. In this case-control study (during 2021-2022), serum levels of total testosterone, free testosterone, and dihydrotestosterone were evaluated in 101 women with hirsutism and 101 healthy women. Hormonal levels were measured with chemiluminescent immunoassay method. Age and hormonal levels in each group, body mass index, menstrual status, complaint of decreased scalp hair density, and ovarian ultrasound findings in hirsutism group were collected and analyzed. There was significant difference in free testosterone and dihydrotestosterone levels (P < 0.001) and no significant difference in total testosterone level between two groups (P = 0.628). Dihydrotestosterone level was significantly higher in women with hirsutism with menses irregularity, complaint of decreased scalp hair density, and presence of polycystic ovary on ultrasound (P < 0.05). Measuring dihydrotestosterone level is not considered in routine evaluation of hirsutism, but we think that this significant difference shows that elevated level of dihydrotestosterone hormone in women with hirsutism is an important factor.

PD02-05 SRD5A2 EXPRESSION IS A PREDICTOR OF RESPONSE TO FINASTERIDE IN THE MTOPS TRIAL

You have accessJournal of UrologyCME1 Apr 2023PD02-05 SRD5A2 EXPRESSION IS A PREDICTOR OF RESPONSE TO FINASTERIDE IN THE MTOPS TRIAL Ra'ad Al-Faouri, Christina Sharkey, Zongwei Wang, and Aria F. Olumi Ra'ad Al-FaouriRa'ad Al-Faouri More articles by this author , Christina SharkeyChristina Sharkey More articles by this author , Zongwei WangZongwei Wang More articles by this author , and Aria F. OlumiAria F. Olumi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The Medical Therapy Of Prostatic Symptoms (MTOPS) study was a multi-center, randomized, controlled clinical trial conducted between 1995 and 2001 aiming to evaluate the effect of finasteride, doxazosin, or a combination of both drugs on the progression of urinary symptoms in men with benign prostatic hyperplasia (BPH). We have demonstrated that 30% of adult prostates do not express SRD5A2 through epigenetic regulation, enabling us to postulate that expression of SRD5A2 may be related to response to finasteride. Prostate biopsies and clinical data from 82 MTOPS trial participants were obtained to test the correlation between baseline expression of SRD5A2 and the response to medical treatment with finasteride. METHODS: We classified men based on changing their AUA symptom score (AUA SS) into good responders (change of AUASS ≤-12) and poor responders (change of AUASS ≥-2). Using immunoreactive score system (IRS score), we quantified the expression of SRD5A2 in the biopsies. We compared baseline age, demographics, AUA SS, BMI, serum dihydrotestosterone (DHT) between men in the two groups. RESULTS: There was no significant difference in TPV between the two groups. Men in the 5ARI good response group were found to have higher expression of SRD5A2 compared to men in the 5ARI poor response group (p-value <0.007). In addition, there was a statistically significant correlation between the expression of SRD5A2 and the 5-year change in AUASS (Pearson's correlation coefficient: -0.4279, p-value: 0.02). In a multiple linear regression model that adjusted for baseline AUA SS, baseline total prostate volume, baseline serum DHT level, age, and BMI, men with higher expression of SRD5A2 still had better response to finasteride with better improvement of urinary symptoms as reflected by AUA symptoms scores. CONCLUSIONS: The MTOPS study was a significant milestone in the curation BPH medical management. Since expression of SRD5A2 is epigenetically regulated during adulthood, our analysis of the biopsies and clinical data provided from the trial shines a light on the importance of SRD5A2 activity and response to 5-ARI therapy. The level of response to 5-ARI therapy correlated to higher SRD5A2 expression. This may contribute to precision medicine by predicting men that are most likely to benefit from tailored therapy by 5-ARI. Source of Funding: NIH: R01DK124502; X01DK131477 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e70 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ra'ad Al-Faouri More articles by this author Christina Sharkey More articles by this author Zongwei Wang More articles by this author Aria F. Olumi More articles by this author Expand All Advertisement PDF downloadLoading ...

Therapeutic Potentiality of Celtis choseniana Nakai on Androgenic Alopecia through Repression of Androgen Action and Modulation of Wnt/β-catenin Signaling

In this study, we investigated the efficacy of Celtis choseniana Nakai (C. choseniana) as complementary herbal medicine to ameliorate androgenic alopecia (AGA). The effects of C. choseniana on AGA were evaluated using testosterone propionate-induced AGA mouse model and dihydrotestosterone-treated human hair follicle dermal papilla cells. In vivo, C. choseniana treatment deactivated androgen signaling by reducing the concentration of serum dihydrotestosterone level and expressions of 5α-reductase 2 and androgen receptor. Next, C. choseniana treatment increased the hair regrowth rate. Histological studies demonstrated that C. choseniana induced the anagen phase in testosterone propionate-induced AGA mouse model. Cellular proliferation was promoted by C. choseniana treatment via increasing the expression of proliferation factors, such as proliferating cell nuclear antigen and cyclin D1. Furthermore, C. choseniana treatment increased the expression of proteins related to the Wnt/β-catenin signaling pathway. In addition, dickkopf-1, a Wnt inhibitor, was downregulated with C. choseniana treatment. Likewise, C. choseniana treatment promoted cellular proliferation in vitro. This study demonstrated the inhibitory effect of C. choseniana on androgen-induced AGA. Moreover, C. choseniana induced activation of Wnt/β-catenin signaling, resulting in prolonged anagen and cellular proliferation. Therefore, we suggest that C. choseniana can be used as a therapeutic agent to alleviate AGA.

Cinnamomum cassia and Rosa laevigata Mixture Improves Benign Prostatic Hyperplasia in Rats by Regulating Androgen Receptor Signaling and Apoptosis.

Benign prostatic hyperplasia (BPH) is the most common condition in elderly men that is characterized by an increase in the size of the prostate gland. Cinnamomum cassia and Rosa laevigata have been reported to treat the symptoms associated with BPH. The aim of this study was to evaluate the effects of HT080, an herbal extract of C. cassia and R. laevigata, on a testosterone propionate (TP)-induced BPH rat model. The rats received a daily subcutaneous injection of TP (3 mg/kg) for 4 weeks to induce BPH. Rats were divided into four groups: group 1 (sham), group 2 (BPH, TP alone), group 3 (Fina, TP + finasteride 1 mg/kg/day), and group 4 (HT080, TP + HT080 200 mg/kg/day). At the end of the experiment, all rats were sacrificed, and their prostate glands were removed, weighed, and subjected to histopathological examination and western blot analyses. Serum testosterone and dihydrotestosterone (DHT) levels were determined. In addition, serum alanine and aspartate aminotransferase levels were measured to evaluate the toxicity in the liver. The Hershberger bioassay was also conducted to investigate the effects of HT080 on androgenic and antiandrogenic activities. In the BPH model, the prostate weight, prostate index, prostate epithelial thickness, and serum testosterone and DHT levels in the HT080 group were significantly reduced compared to the BPH group. Histological studies showed that HT080 reduced prostatic hyperplasia. The protein expression of androgen receptor from the HT080 group was significantly reduced in comparison with the BPH group (p < 0.05). HT080 also induced apoptosis by regulating Bcl-2 and Bax expression. In addition, HT080 showed no toxicity in the liver and did not exhibit androgenic and antiandrogenic activities. Our finding revealed that HT080 can be a potential candidate for the treatment of BPH by regulating androgen receptor signaling and apoptosis.

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.

Serum dihydrotestosterone levels are associated with adverse myocardial remodeling in patients with severe aortic valve stenosis before and after aortic valve replacement.

Animal studies show a pivotal role of dihydrotestosterone (DHT) in pressure overload-induced myocardial hypertrophy and dysfunction. The aim of our study was to evaluate the role of DHT levels and myocardial hypertrophy and myocardial protein expression in patients with severe aortic valve stenosis (AS). Forty-three patients [median age 68 (41-80) yr] with severe AS and indication for surgical aortic valve replacement (SAVR) were prospectively enrolled. Cardiac magnetic resonance imaging including analysis of left ventricular muscle mass (LVM), fibrosis and function, and laboratory tests including serum DHT levels were performed before and after SAVR. During SAVR, left ventricular (LV) biopsies were performed for proteomic profiling. Serum DHT levels correlated positively with indexed LVM (LVMi, R = 0.64, P = 0.0001) and fibrosis (R = 0.49, P = 0.0065) and inversely with LV function (R = -0.42, P = 0.005) in patients with severe AS. DHT levels were associated with higher abundance of the hypertrophy (moesin, R = 0.52, P = 0.0083)- and fibrosis (vimentin, R = 0.41, P = 0.039)-associated proteins from LV myocardial biopsies. Higher serum DHT levels preoperatively were associated with reduced LV function (ejection fraction, R = -0.34, P = 0.035; circulatory efficiency, R = -0.46, P = 0.012; and global longitudinal strain, R = 0.49, P = 0.01) and increased fibrosis (R = 0.55, P = 0.0022) after SAVR. Serum DHT levels were associated with adverse myocardial remodeling and higher abundance in hypertrophy- and fibrosis-associated proteins in patients with severe AS. DHT may be a target to prevent or attenuate adverse myocardial remodeling in patients with pressure overload due to AS.NEW & NOTEWORTHY Serum dihydrotestosterone (DHT) levels correlated positively with the degree of hypertrophy, fibrosis, and dysfunction from cardiac magnetic resonance imaging in female and male patients with aortic valve stenosis. Left ventricular proteome profiling had been performed in this patient cohort and an association between serum DHT levels and the abundance of the hypertrophy-associated protein moesin and the fibrosis-associated protein vimentin was found.

What's New in Therapy for Male Androgenetic Alopecia?

Male androgenetic alopecia is a common condition and represents a major concern for patients who experience this condition. While there are different treatments to stop hair loss and improve hair density, the 5-alpha reductase inhibitors have demonstrated to be effective in improving androgenetic alopecia in men and can maintain a positive response for many years. Oral finasteride 1mg is a US FDA-approved option, but dutasteride 0.5 mg has been proven to induce better responses, especially in the frontal area. Both have been shown to be safe in clinical trials but there is widespread concern about sexual adverse effects among patients. The use of topical finasteride has increased during the last few years as a useful option to avoid systemic therapy. The efficacy of topical finasteride 0.25% daily has been demonstrated in clinical trials, with a less marked decrease in serum dihydrotestosterone levels than with oral intake. Mesotherapy with dutasteride has also become more widespread recently, although evidence of its effectiveness is limited to retrospective studies in real clinical practice. The use of oral minoxidil in androgenetic alopecia has not been approved by the FDA, however several clinical studies have shown that it is an effective treatment option. The initial dose recommended to treat male hair loss is 2.5 mg daily, although the dose is frequently increased to 5 mg daily. The main adverse effect of oral minoxidil is hypertrichosis, followed by dizziness or lower limb edema, which are much less common. Platelet-rich plasma is a non-pharmacological option to treat male androgenetic alopecia, with some clinical trials demonstrating an improvement in hair count after several months. Among the published studies, the main limitation to compare its efficacy is the heterogeneity of the procedure. The most frequent regimens propose treatment every 4 weeks for 3 months initially to assess the individual response. Another treatment alternative is the use of light devices with wavelengths of between 630 and 660 nm, known as low-level laser therapy. These devices can be used at home every day for 15-30min. Their efficacy has been shown in a limited number of clinical trials; however, there is a lack of evidence about the efficacy of these devices compared with other medical options or as a complementary therapy in hair loss. The pipeline of potential new treatments for male androgenetic alopecia is strong. Pyrilutamide and GT20029 are being studied as topical antagonists of the androgen receptor, while cetirizine is another topical option with some initial promising results. Furthermore, according to isolated studies with heterogeneous treatment schemes, the use of botulinum toxin in the scalp might improve androgenetic alopecia, and lastly, scalp threading might increase the total hair count as growth factors are released during implantation.

Eriochloa villosa Alleviates Progression of Benign Prostatic Hyperplasia in vitro and in vivo.

IntroductionBenign prostatic hyperplasia (BPH) is a non-neoplastic proliferative disease of the prostate. Eriochloa villosa (EV) reportedly possesses various pharmacological activities, including anti-lipase activity and modulation of various antioxidative enzymes. In this study, we investigate the therapeutic potential of EV against BPH in a testosterone-induced BPH rat model.MethodsRats were subjected to a daily subcutaneous injection of testosterone (3 mg kg−1) for 4 weeks to induce BPH. Along with testosterone, rats in the treatment group were administered finasteride (10 mg kg−1) or EV (150 mg kg−1) via oral gavage. Prostatic cancer (LNCaP) cell line was used to examine the effect of EV.ResultsFinasteride and EV significantly decrease the relative prostate weight, serum levels of dihydrotestosterone and testosterone, and prostate epithelial thickness. Testosterone injection induced prostatic hyperplasia and proliferating cell nuclear antigen expression; however, EV treatment significantly attenuated these effects. Moreover, finasteride- and EV-treated rats exhibit an increase in the number of TUNEL-positive cells and reduced Bcl-2 expression in the prostate tissues compared with the testosterone-treated animals. Furthermore, EV suppresses inflammatory cytokines, including interleukin (IL)-6 and IL-8, in the prostate tissues. Meanwhile, the expression of inflammatory mediator cyclooxygenase-2 is consistently upregulated in testosterone-treated rats, whereas EV treatment significantly reverses this effect. Notably, EV treatment suppresses malondialdehyde (MDA) levels and upregulates testosterone-induced catalase (CAT) expression. In addition, EV suppresses expression of androgen receptor (AR) and prostate-specific antigen (PSA) induced by testosterone in LNCaP cells.ConclusionThe present study results suggest that EV regulates prostatic proliferation, apoptosis, response to inflammation, and oxidative stress in the BPH rat model, and may, therefore, serve as a useful therapeutic agent for BPH.

Associations between serum dihydrotestosterone levels, lipid parameters &amp; anthropometric measurements in male patients with type 2 diabetes mellitus

Background: Male fertility is affected by the metabolic and hormonal dysregulation brought on by Diabetes Mellitus, a metabolic illness, particularly in the hypothalamus-pituitary testicular axis. However, there is little proof that endocrinopathy causes diabetic men's infertility and low testosterone levels. It is well established that Type 2 Diabetes causes dyslipidemia &amp; obesity by lowering serum testosterone levels. However, there isn't much research on DHT, the most potent androgen, and its relationship to male lipid profiles. Methods: The study was carried out at Teerthanker Mahaveer Medical College and Research Centre, Moradabad, in the Department of Physiology and Medicine &amp; Department of Physiology Santosh Medical College, Ghaziabad. A total of 210 samples—105 from type 2 diabetics and 105 from controls—were included in the study. Using conventional biochemical techniques, Lipid parameters [HDL, LDL, VLDL &amp;TC], serum DHT, Data analysis was done with SPSS 26. [ trial version]. Results: The levels of serum dihydrotestosterone were significantly lower in diabetic cases than in healthy controls [439.26 ± 257.87pg/ml vs 230.66 ± 182.02pg/ml, p=0.001]. 90 percent of Type 2 diabetics were found to have subnormal levels, as opposed to just 10 percent of controls.

In utero exposure to dietary emulsifier alters the behavioral activity in offspring

ObjectivePediatric mental health disorder is a combination of neuroinflammatory conditions with unknown etiology and currently, there are less awareness on the impacts of food additives on pediatric neuroinflammatory conditions and adolescent mental health disorders. Food additives such as dietary emulsifier (DE) (polysorbate 80, carrageenan and maltodextrin) are added to a variety of processed foods, and their consumption has increased dramatically worldwide which could be a risk factor for pediatric mental health disorders. Therefore, there is a critical need to understand the impact of maternal exposure to food additives associated pediatric mental health and the underlying mechanism.Materials and MethodsBehavioral testing such as tail flick assay, radial arm, rotarod and hot plate assay was done on the offspring from both control and DE exposed mice for the impaired motor activity, pain sensitivity and cognitive behavior. Colonic microbial composition was determined through 16sRNA pyrosequencing of fecal DNA samples from control and in utero DE‐exposed offspring. Level of pro inflammatory cytokines in the colon tissue as well as the serum sample was measured using Multianalyte cytokine assay kit from Qiagen.Summary of ResultsOur results show that in utero exposure to DE leads to decreased brain sizes and impaired motor learning in the offspring. Additionally, in utero exposure to DE leads to decreased pain sensitivity as a sign of stress in offspring. In utero exposure to DE shows on onset of cognitive impairment in offspring. In utero exposure to DE leads to an elevated M1 macrophage cytokine profile and CLGI symptoms in the gastrointestinal tract of offspring. In utero exposure to DE leads to gut dysbiosis in offspring. Among the DE‐exposed adolescents, the male offspring had significantly higher impact on these parameters compared to the DE‐exposed female offspring. In utero exposure to DE leads to imbalance in serum levels of dihydrotestosterone (DHT) and estradiol (E2) in the Offspring.ConclusionOur data suggest that maternal exposure to food additive is associated with the male biased cognitive impairment and neurobehavioral changes in the offspring. In future, we will determine the specific mechanism responsible for the sex specific alternation in offspring born to DE exposed mother to develop a preventative and therapeutic strategies.

Up-regulation of androgen receptor by heat shock protein 27 and miR-1 induces pathogenesis of androgenic alopecia.

The pathogenesis of androgenetic alopecia (AGA) is related to the level of androgen and its metabolic pathways. The binding of androgen and androgen receptor (AR) depends on the assistance of heat shock protein 27 (HSP27). HSP27 combined with microRNAs (miR)-1 can regulate AR levels. However, it is not clear whether HSP27 and miR-1 jointly participate in the pathogenesis of AGA. This study aims to investigate the role of AR up-regulation in the pathogenesis of AGA and underlying mechanisms. A total of 46 male AGA patients (AGA group), who admitted to the First Affiliated Hospital of Guangzhou Medical University from September 2019 to February 2020, and 52 healthy controls admitted to the same period were enrolled in this study. Serum levels of dihydrotestosterone (DHT) and HSP27 in patients and healthy controls were measured by ELISA. Western blotting was used to detect the protein expression of HSP27 and AR in scalp tissues of patients and the healthy controls. The levels of HSP27, AR, and miR-1 were analyzed using real-time PCR. Human dermal papilla cells were transfected with HSP27 siRNA to inhibit the expression of HSP27. MiR-1 and miR-1 inhibitors were transfected simultaneously or separately into cells and then the changes in AR protein expression were detected. The levels of DHT and HSP27 in the AGA group were (361.4±187.7) pg/mL and (89.4±21.8) ng/mL, respectively, which were higher than those in the control group [(281.8±176.6) pg/mL and (41.2±13.7) ng/mL, both P<0.05]. However, there was no significant difference in serum HSP27 and AR levels among AGA patients with different degrees of hair loss (P>0.05). Correlation analysis showed that there was a positive correlation between HSP27 level and DHT level in the AGA patients (P<0.05). The level of HSP27 mRNA in scalp tissue was negatively correlated with that of miR-1 mRNA (P<0.05). Compared with the control group, the levels of HSP27 protein, AR protein, HSP27 mRNA, and AR mRNA in scalp tissues of AGA group were significantly increased (P<0.05). The up-regulation of HSP27 in scalp tissues of AGA patients was closely related to the increased levels of AR. However, the level of miR-1 in scalp tissues of AGA patients was significantly down-regulated, contrary to the expression of AR (P<0.05). Further in cell studies showed that inhibition of HSP27 or miR-1 expression in human dermal papilla cells could inhibit the expression of AR, and inhibition of both HSP27 and miR-1 expression was found to have an accumulative effect on AR, with statistically significant differences (all P<0.05). HSP27 could combine with miR-1 to up-regulate AR levels, which is closely related to the development of AGA.

Age related changes in serum dihydrotestosterone levels among type 2 diabetic males

Background: Interest in the physiological range of androgens in middle-aged men has recently increased since many illnesses, deaths, or male-specific disturbances are linked to androgen deficiency. It is yet unknown how dihydrotestosterone (DHT) levels have changed over time in the Indian population. Aims and Objectives: The purpose of the study was to measure the levels of DHT in males as age. The absence of data on DHT levels in ageing males in the Indian population would allow for comparisons with future studies from other subcontinents. Materials and Methods: In this study, residents of Moradabad, Uttar Pradesh, are the subjects of an observational and comparative case–control study. Results: A total of 210 samples were collected, including 105 diabetic men and 105 controls, samples were divided into each of the three age brackets 30–40 years, 40–50 years, and 50–60 years. Compared to controls, who had a total mean DHT of 446.76 ± 265.31 pg/ml, diabetics’ total mean DHT was lower at 230.66 ± 182.02 pg/ml. The same was seen when diabetic samples and controls were compared by age groups. When age groups of diabetic samples and controls were compared there was no decline with the age group, there was a non-significant association in their comparison. When all of the samples were included, there was a non-significant reduction in DHT levels as the age groups progressed, although a decline was observed. Conclusions: Age-related declines in serum DHT hormone levels occur over time but are not very significant.

Electroacupuncture improves metabolic and ovarian function in a rat model of polycystic ovary syndrome by decreasing white adipose tissue, increasing brown adipose tissue, and modulating the gut microbiota.

Polycystic ovary syndrome (PCOS) affects 8%-15% of reproductive-age women and is associated with reproductive disorders, abdominal obesity, hyperinsulinemia, insulin resistance, type 2 diabetes, and cardiovascular diseases. Acupuncture, as a traditional physical therapy method, could affect various metabolic disorders such as obesity, hyperplasia, gout, and cardiovascular and cerebrovascular diseases in clinical practice. Moreover, electroacupuncture (EA) has been shown to decrease body weight in rats with PCOS; however, the mechanism of weight loss and the relationship between adipose tissue and gut microbiota remain unclear. To explore the effect and mechanism of EA on white and brown adipose tissues and gut microbiota, and its follow-up effect on reproductive function, in a rat model of PCOS. Daily EA treatment was administered at ST29 and SP6 in a dihydrotestosterone (DHT)-induced PCOS-like rat model (PCOS + EA group). Effects of EA on in vivo and in vitro adipose volume and weight, organ weight coefficients, body weight, hormonal profiles, and estrous cyclicity were measured, and compared with untreated PCOS model rats (PCOS group) and healthy rats (control group). Microbial DNA was extracted from the fecal samples to analyze group abundance and diversity. EA improved estrous cyclicity, decreased body weight, decreased visceral and subcutaneous fat content, and increased brown adipose tissue weight. EA also normalized serum DHT and progesterone levels and improved glucose tolerance. There were few significant differences in the composition or diversity of the gut microbiota between control, PCOS, and PCOS + EA groups, except for the relative abundances of Tenericutes at the phylum level and Prevotella_9 at the genus level, which were significantly different in the PCOS group before and after EA treatment. Both are important microflora, strongly related to body weight. EA regulated the metabolic disorders and improved reproductive function in this PCOS-like rat model by adjusting visceral fat and brown fat, as well as intestinal flora.

Chemical profiles of the active fraction from Prinsepia utilis Royle leaves and its anti-benign prostatic hyperplasia evaluation in animal models

BackgroundThe Prinsepia utilis Royle leaves (P. utilis) is a folk herb used for benign prostatic hyperplasia (BPH) control by ethnic minorities for centuries in China with rich in resources. Our previous studies have confirmed the anti-BPH effect of its water extract (QCJ) and the active fraction (Fr. B) separated from the QCJ by animal test. The Fr. B from P. utilis should be a potential candidate for BPH control.MethodsIn this study, the chemical ingredients of Fr. B were identified by UPLC-QTOF-MS, and quantified by HPLC. Murine animal models were divided into 8 groups, Sham rats, BPH rats, BPH rats administered with finasteride (1 mg/kg), BPH rats administered with Pule’an (460 mg/kg), BPH rats administered with low, high dosage of QCJ (860 mg/kg, 2580 mg/kg respectively), BPH rats administered with low, high dosage of Fr. B (160 mg/kg, 480 mg/kg respectively). The expression of vascular endothelial growth factor (VEGF) in the prostate tissue of rats was tested, and serum levels of dihydrotestosterone (DHT), testosterone (T), estradiol (E2), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and total superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), malondialdehyde (MDA) in prostate homogenate were measured. One-way ANOVA followed by LSD was used for statistical analysis.ResultsThe BPH rats treated by Fr. B exhibited significant reductions of VEGF and MDA levels, as well as significant increases of SOD, GSH-Px and CAT in the prostate tissue after 28 day administration (P < 0.05). Moreover, Fr. B significantly reduced DHT, DHT/E2 ratio, TNF-α, while increased T levels in serum of BPH rats (P < 0.05). UPLC-QTOF-MS analysis revealed 10 flavonoids as the key constituents of this fraction, which accounted for 54.96% of all substance of Fr. B. The relative contents of compound 1, 2 are 11.1%, 13% in Fr. B respectively.ConclusionsThese results indicated that the Fr. B obtained from P. utilis alleviated the symptoms of BPH rats through multiple mechanisms including reduction of DHT/E2 ratio, inhibition of growth factor, anti-inflammation and anti-oxidation, in which flavonoids might be the key constituents. It supported the hypothesis that the Fr. B should be further explored as a candidate for BPH patients.