5α-reductase Research Articles

Genomic Markers and Personalized Medicine in Androgenetic Alopecia: A Comprehensive Review

Androgenetic alopecia (AGA) is the most common form of hair loss, significantly affecting both men and women worldwide. Characterized by progressive hair thinning and loss, AGA is primarily mediated by dihydrotestosterone (DHT). Recent research has identified numerous single-nucleotide polymorphisms (SNPs) associated with AGA, particularly in genes involved in androgen metabolism, prostaglandin pathways, and vasodilation. These genetic markers offer insights into AGA pathophysiology and potential therapeutic targets. Pharmacogenetics, the study of how genetic variations influence drug response, holds promise for personalized AGA treatment. Identifying SNPs that affect the efficacy of treatments like minoxidil and finasteride enables the development of tailored therapeutic strategies. For instance, genetic variants in the SRD5A2 gene, which affects DHT metabolism, can predict responsiveness to 5-alpha-reductase inhibitors. Beyond pharmacogenetics, RNA interference (RNAi) technologies, e.g., small interfering RNAs (siRNAs), present new therapeutic avenues. Studies have shown the efficacy of RNAi-based treatments in targeting androgen receptors, promoting hair growth in AGA models. Integrating genetic and pharmacogenetic research into clinical practice can transform AGA management, enhancing treatment efficacy and patient outcomes. In conclusion, genetic and pharmacogenetic insights are crucial for developing personalized treatments for AGA, while emerging RNAi technologies offer promising new interventions. These advancements represent significant steps toward more effective and individualized AGA therapies.

Screening for carriers of the SRD5A2 gene mutation 5-alpha-reductase 2 deficiency in Vietnamese pregnant wome

Objective: To describe the percentage of people who carry the SRD5A2 gene mutation causing 5-alpha-reductase 2 deficiency and the characteristics of their mutated variants in Vietnamese pregnant women. Subjects and methods: A cross-sectional descriptive study was conducted on 8,464 pregnant women who visited and agreed to perform a screening test for gene carriers related to recessive genetic conditions at the Institute of DNA Technology and Genetic Analysis. All information about pregnant women including maternal age, gestational age, number of pregnancies and SRD5A2 gene mutation test results were collected. Results: Of 8,464 pregnant women participating in the study, 315 pregnant women (3.72%) carried pathogenic mutations on the SRD5A2gene. The c.680G>A mutation (p.Arg227Gln) is the most common of the SRD5A2 gene mutations detected. Conclusion: The rate of pregnant women carrying SRD5A2 gene mutations is 3.72%, indicating the high prevalence of this gene mutation in Vietnamese pregnant women. In the future, it is necessary to expand and develop SRD5A2 gene mutation screening programs in Vietnamese pregnant women.

The impact of preoperative 5-alpha reductase inhibitors on functional outcomes and health-related quality of life following radical prostatectomy – A propensity score matched longitudinal study

ObjectivesWhile the impact of treatment with 5-alpha Reductase Inhibitors (5-ARI) on the risk of cancer-related mortality in men with prostate cancer (PC) has been extensively studied, little is known about the impact of preoperative 5-ARI use on patient-reported outcomes (PROs) following radical prostatectomy (RP).MethodsWithin our prospectively maintained institutional database of 5899 patients treated with RP for PC (2008– 2021), 99 patients with preoperative 5-ARI therapy were identified. A 1:4 propensity-score matched analysis of 442 men (n = 90 5-ARI, n = 352 no 5-ARI) was conducted. Primary endpoint was continence recovery using daily pad usage and ICIQ-SF. Health-related quality of life (HRQOL) was assessed using the validated EORTC QLQ-C30 and PR25 questionnaires. Multivariable Cox-regression-models tested the effect of preoperative 5-ARI treatment on continence-recovery (p < 0.05).ResultsPatients were followed up perioperatively, followed by annual assessments up to 60mo postoperatively. Preoperative mean ICIQ-SF score (2.2 vs. 0.9) was significantly higher in the 5-ARI cohort (p = 0.006). 24mo postoperatively, 68.6% (no 5-ARI) vs. 55.7% (5-ARI) had full continence recovery (p = 0.002). Multivariable Cox regression analysis, revealed preoperative 5-ARI treatment as an independent predictor for impaired continence recovery (HR 0.50, 95% CI 0.27–0.94, p = 0.03) In line, general HRQOL was significantly higher for patients without 5-ARI only up to 24mo postoperatively (70.6 vs. 61.2, p = 0.045). There was no significant impact of preoperative 5-ARI treatment on erectile function, biochemical recurrence-free survival and metastasis-free survival.ConclusionsPre-RP 5-ARI treatment was associated with impaired continence outcomes starting 24mo postoperatively, suggesting that preoperative 5-ARI treatment can impair the long-term urinary function recovery following RP.

Effects of Biomaterials Derived from Germinated Hemp Seeds on Stressed Hair Stem Cells and Immune Cells.

Androgenetic alopecia is a genetic disorder that commonly causes progressive hair loss in men, leading to diminished self-esteem. Although cannabinoids extracted from Cannabis sativa are used in hair loss treatments, no study has evaluated the effects of germinated hemp seed extract (GHSE) and exosomes derived from the calli of germinated hemp seeds on alopecia. Therefore, this study aimed to demonstrate their preventive effects against alopecia using various methodologies, including quantitative PCR, flow cytometry, ELISA, and immunocytochemistry. Our research highlights the preventive functions of GHSE (GE2000: 2000 µg/mL) and exosomes from the calli of germinated hemp seeds (E40: 40 μg/mL) in three biochemical categories: genetic modulation in hair follicle dermal papilla stem cells (HFDPSCs), cellular differentiation, and immune system modulation. Upon exposure to dihydrotestosterone (DT), both biomaterials upregulated genes preventing alopecia (Wnt, β-catenin, and TCF) in HFDPSCs and suppressed genes activating alopecia (STAT1, 5α-reductase type 1, IL-15R). Additionally, they suppressed alopecia-related genes (NKG2DL, IL2-Rβ, JAK1, STAT1) in CD8+ T cells. Notably, E40 exhibited more pronounced effects compared to GE2000. Consequently, both E40 and GE2000 effectively mitigated DT-induced stress, activating mechanisms promoting hair formation. Given the limited research on alopecia using these materials, their pharmaceutical development promises significant economic and health benefits.

External validation of the barcelona magnetic resonance imaging predictive model for detecting significant prostate cancer including men receiving 5-alpha reductase inhibitors

PurposeTo validate the Barcelona-magnetic resonance imaging predictive model (BCN-MRI PM) for clinically significant prostate cancer (csPCa) in Catalonia, a Spanish region with 7.9 million inhabitants. Additionally, the BCN-MRI PM is validated in men receiving 5-alpha reductase inhibitors (5-ARI).Materials and methodsA population of 2,212 men with prostate-specific antigen serum level > 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and targeted and/or systematic biopsies in the year 2022, at ten participant centers of the Catalonian csPCa early detection program, were selected. 120 individuals (5.7%) were identified as receiving 5-ARI treatment for longer than a year. The risk of csPCa was retrospectively assessed with the Barcelona-risk calculator 2 (BCN-RC 2). Men undergoing 5-ARI treatment for less than a year were excluded. CsPCa was defined when the grade group was ≥ 2.ResultsThe area under the curve of the BCN-MRI PM in 5-ARI naïve men was 0.824 (95% CI 0.783–0.842) and 0.849 (0.806–0.916) in those receiving 5-ARI treatment, p 0.475. Specificities at 100, 97.5, and 95% sensitivity thresholds were to 2.7, 29.3, and 39% in 5-ARI naïve men, while 43.5, 46.4, and 47.8%, respectively in 5-ARI users. The application of BCN-MRI PM would result in a reduction of 23.8% of prostate biopsies missing 5% of csPCa in 5-ARI naïve men, while reducing 25% of prostate biopsies without missing csPCa in 5-ARI users.ConclusionsThe BCN-MRI PM has achieved successful validation in Catalonia and, notably, for the first time, in men undergoing 5-ARI treatment.

Effects of Camellia oleifera seed shell polyphenols and 1,3,6-tri-O-galloylglucose on androgenic alopecia via inhibiting 5a-reductase and regulating Wnt/β-catenin pathway

Androgenetic alopecia (AGA) is the leading cause of hair loss in adults. Its pathogenesis remains unclear, but studies have shown that the androgen-mediated 5α-reductase-AR receptor pathway and the Wnt/β-catenin signaling pathway play significant roles. Camellia oleifera is an oil plant, and its fruits have been documented in folklore as having a hair cleansing effect and preventing hair loss. In this study, we used UPLC-Q-TOF-MS/MS to identify the structure of the substances contained in the polyphenols of Camellia oleifera seed shell. These polyphenols are mainly used for shampooing and anti-hair loss purposes. Next, we used molecular docking technology to dock 41 polyphenols and steroidal 5 alpha reductase 2 (SRD5A2). We found that the docking scores and docking sites of 1,3,6-tri-O-galloylglucose (TGG) and finasteride were similar. We constructed a mouse model of DHT-induced AGA to evaluate the effects of Camellia oleifera seed shell polyphenols (CSSP) and TGG in vivo. Treatment with CSSP and TGG alleviated alopecia symptoms and reduced DHT levels. Additionally, CSSP and TGG were able to reduce androgen levels by inhibiting the SRD5A2-AR receptor signaling pathway. Furthermore, by regulating the secretion of growth factors and activating the Wnt/β-catenin signaling pathway, CSSP and TGG were able to extend the duration of hair growth. In conclusion, our study showed that CSSP and TGG can improve AGA in C57BL/6 J mice and reduce the effect of androgen on hair follicle through the two signaling pathways mentioned above. This provides new insights into the material basis and mechanism of the treatment of AGA by CSSP.

Evaluation of Tamsulosin 0.4 mg versus 0.8 mg in Management of Patients Suffering from Lower Urinary Tract Symptoms Due to Benign Prostatic Hyperplasia

Abstract Introduction Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) are common among older men. Beside watchful waiting and surgery, medical therapy includes alpha adrenergic blockers, 5 alpha reductase inhibitors, and phytotherapy. Alpha blockers are considered to be the main treatment for BPH-associated LUTS depending on the evidence that prostatic smooth muscle contraction is responsible for bladder outlet obstruction via alpha adrenergic receptor- mediated mechanism. Tamsulosin is a super selective alpha blocker. Improvement of LUTS can be assessed by maximum flow rate (Qmax), average flow rate (Qavg), post void residual (PVR) urine volume and international prostate symptom score questionnaire (IPSS). Objectives To compare the efficacy and the safety of Tamsulosin 0.4 mg/day and 0.8 mg/day in patients suffering from lower urinary tract symptoms due to benign prostatic hyperplasia. Patients and Methods A Prospective Interventional, double-blinded, controlled study was carried out on 93 patients who met the criteria and divided randomly into 2 groups; group A for Tamsulosin 0.4 mg/day and group B for Tamsulosin 0.8 mg/day. International prostate symptom score, Post void residual urine volume, and maximum flow rate of urine were assessed before and after 4 weeks of treatment. Results Both study groups showed a significant reduction in storage sub-score but only frequency was significantly reduced in group B (P &amp;lt; 0.001). On the other hand, Tamsulosin 0.8 mg was superior to Tamsulosin 0.4 mg regarding voiding sub score except for straining (P = 0.325). Accordingly, the total international prostate symptom score was significantly improved in group B (P &amp;lt; 0.001). Furthermore, maximum flow rate and post-void residual urine volume were notably improved with Tamsulosin 0.8 mg compared to Tamsulosin 0.4 mg (P &amp;lt; 0.001). Although the adverse events; such as headache, orthostatic hypotension, and retrograde ejaculation were more frequent, but not significant, to occur with Tamsulosin 0.8 mg, only dizziness was noted to be significant. Conclusion Tamsulosin 0.8 mg has shown better outcomes in treating patients who suffer from lower urinary tract symptoms due to benign prostatic hyperplasia than Tamsulosin 0.4 mg, and besides that, it is well tolerated.

Long-Term Water Vapor Thermal Therapy Outcomes Across a Broad Range of Prostate Volumes.

Water vapor thermal therapy (WVTT) is a minimally invasive therapy designed to treat lower urinary tract symptoms associated with benign prostatic hyperplasia. Long-term outcomes with large (>80 cc) and small (<30 cc) prostate volumes (PVs) remain limited. We report 48-month outcomes for a multiethnic cohort of WVTT-treated men, stratified by PV. In this single-center retrospective study, patients were stratified by PV: < 30 cc, 30 to 80 cc, or > 80 cc. Outcome measures, including International Prostate Symptom Score, quality of life, International Index of Erectile Function, medication usage, and adverse events, were analyzed at baseline and at 1-, 3-, 6-, 12-, 24-, 36-, and/or 48-month follow-up. Two hundred fifty-two patients met inclusion; 35 (13.9%) had PVs < 30 cc, 196 (77.8%) had PVs 30 to 80 cc, and 21 (8.3%) had PVs > 80 cc. Most patients were Asian (33.7%) or non-Hispanic Black (29.4%). International Prostate Symptom Score and quality of life improved in all cohorts from baseline at all follow-ups (all P < .05), with no differences between cohorts. International Index of Erectile Function-Orgasmic Function and -Erectile Function domains improved in 30 to 80 cc patients at 48 months. Alpha blocker and/or 5-alpha reductase inhibitor usage decreased at all follow-ups in < 30 cc and 30 to 80 cc patients and remained durable to only 6 months for > 80 cc patients. No significant differences in adverse events or reoperation rates were observed between cohorts. Our study suggests WVTT to be efficacious, durable, and safe in managing lower urinary tract symptoms across PVs, although PV > 80 cc patients may require benign prostatic hyperplasia medication at long-term follow-up. Further research is desired to clarify WVTT's role regarding sexual function and in treating men with larger PVs.

Preparation and Characterization of Dutasteride Nanoparticles as Oral Fast-Dissolving Film

Background: Dutasteride, is a drug whose mechanism of action is inhibition of the enzyme 5-alpha reductase. It has been approved for use in the treatment of benign prostatic hyperplasia. Dutasteride has low solubility and high permeability, which classifies it as Biopharmaceutics classification system class II, according to the Biopharmaceutics Classification System. It has a water solubility of only 0.038 ng/mL and a slow dissolving rate, resulting in its exclusive availability in the market as a formulation contained within soft gelatin capsules. Objective: The aim of this study involves two parts. First, is the enhancement of dutasteride dissolution rate, by the creation of dutasteride nanosuspension, and second is the enhancement of patient compliance by the transformation of this nanosuspension to oral fast-dissolving film, which is characterized by its fast disintegration, stability, and ease of administration. Methods: The solvent anti/solvent precipitation method was used to formulate dutasteride nanosuspension. In addition, dutasteride nanoparticles oral fast dissolving films were prepared by using the solvent casting method. To compare the in vitro release patterns of pure dutasteride film and selected dutasteride nanoparticles film, the statistical analysis for the dissolution investigation was conducted using the model-independent technique (employing similarity factor f2) utilizing a DD solver. The selected dutasteride nanoparticle film was supposed to be the test material, while the pure dutasteride film was supposed to serve as the reference. Results: dutasteride nanosuspension demonstrated a high enhancement of the dissolution rate. In addition, the prepared dutasteride nanoparticles oral fast-dissolving film exhibited a further increase in the rate of dissolution and fast disintegration, and the administration is easy, all of these properties making it a promising dosage form. Conclusion: Nanosuspension is an excellent approach for enhancing the solubility, dissolution rate, and effectiveness of drugs with limited aqueous solubility such as dutasteride. In addition, the oral fast-dissolving film can be considered a promising dosage form that will increase patient compliance due to its high dissolution rate, fast disintegration, and easy administration.

A Potential Pathogenic SRD5A2 Mutation and rs632148, rs523349 and rs522638 Polymorphisms in Increasing the Risk of Syndromic Hypospadias in Indonesian Population

BACKGROUND: Hypospadias, a congenital birth defect in male, is the opening of the urethra located on the ventral side of the penis. Several mutations in SRD5A2 encoding steroid 5 alpha-reductase type 2 protein have been identified in hypospadias and polymorphisms in this gene have been known to be associated with an increased risk of hypospadias. In this study, several crucial molecular analyses of the SRD5A2 gene and the association of the identified variants to the risk of syndromic hypospadias in Indonesian population were conducted.METHODS: Thirty-two isolated and 29 syndromic hypospadias patients were enrolled in this study. DNA was isolated from whole blood for the amplification of all exons and exon-intron boundaries of SRD5A2 by polymerase chain reaction (PCR), followed by Sanger sequencing. In silico analysis was performed using PolyPhen-2, Sorting Intolerant from Tolerant (SIFT) and Align GVGD. Statistical analysis was performed using Chi-squared test.RESULTS: A novel missense mutation c.32T&gt;C/p.Leu11Pro was identified in one isolated hypospadias patient and the in silico analysis predicted the mutation to be pathogenic. Three polymorphisms were identified, two in the non-coding region (c.-62G&gt;C/rs632148 and c.281+15T&gt;C/rs522638) and one in exon-1 (c.265C&gt;G/p.Val89Leu/rs523349). Mutant alleles of these polymorphisms were significantly associated with syndromic hypospadias with odds ratios (OR) of 3.4, 3.13 and 2.54 respectively.CONCLUSION: This study suggests that SRD5A2 mutation is one of the causes of hypospadias in Indonesian population and rs632148, rs523349 and rs522638 polymorphisms are significantly associated with an increased risk of syndromic hypospadias.KEYWORDS: mutation, polymorphism, SRD5A2, syndromic hypospadias

Anti-proliferative effect and mechanisms of Peony pollen on BPH via inhibition of inflammatory factors, oxidative damage and modulation of gut microbiota and SCFAs metabolism

BackgroundPeony pollen (PP) has long been used as a functional food and herbal medicine. However, the potential protective effect and mechanisms of PP on benign prostatic hyperplasia (BPH) are still unclear. This study aims to explore the therapeutic effect and potential mechanisms of PP on BPH. MethodsThe rat model of BPH was induced by subcutaneous injection of testosterone propionate (TP). Meanwhile, the model rats were treated with PP, and physiological and biochemical indexes, the steroid 5 alpha reductase 2 (SRD5A2), proliferating cell nuclear antigen (PCNA) and androgen receptor (AR) expressions, gut microbiota and short-chain fatty acids (SCFAs) were measured. ResultsThe results showed that the wet weight of prostate tissue and the thickness of epithelium decreased treated with PP significantly. In addition, the PP also adjusted the androgen levels, down-regulated the SRD5A2, PCNA and AR expressions, inhibited the expression of inflammatory factors including interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and reduced oxidative damage in BPH rats. It is worth noting that PP can obviously regulate the gut microbiota disorder of BPH rats, increase the abundance of beneficial bacteria (e.g., Romboutsia), reduce the abundance of pathogenic bacteria (e.g., norank_f_Oscillospiraceae), and stimulate the increase of SCFAs content. ConclusionsThese data showed that PP can resist abnormal proliferation of the prostate by down regulation of SRD5A2, PCNA and AR expressions, attenuating oxidation stress and inflammatory damages and directly regulate the gut microbiota, especially the Firmicutes, and increased the level of SCFAs to ameliorate BPH. Therefore, PP might be an excellent natural plant for the development of BPH-related drugs or dietary supplements.

Adverse effects of the 5-alpha-reductase inhibitor finasteride on Daphnia magna: Endocrine system and lipid metabolism disruption

Finasteride, a steroid 5-alpha reductase inhibitor, is commonly used for the treatment of benign prostatic hyperplasia and hair loss. However, despite continued use, its environmental implications have not been thoroughly investigated. Thus, we investigated the acute and chronic adverse impacts of finasteride on Daphnia magna, a crucial planktonic crustacean in freshwater ecosystems selected as bioindicator organism for understanding the ecotoxicological effects. Chronic exposure (for 23 days) to finasteride negatively affected development and reproduction, leading to reduced fecundity, delayed first brood, reduced growth, and reduced neonate size. Additionally, acute exposure (< 24 h) caused decreased expression levels of genes crucial for reproduction and development, especially EcR-A/B (ecdysone receptors), Jhe (juvenile hormone esterase), and Vtg2 (vitellogenin), with oxidative stress-related genes. Untargeted lipidomics/metabolomic analyses revealed lipidomic alteration, including 19 upregulated and 4 downregulated enriched lipid ontology categories, and confirmed downregulation of metabolites. Pathway analysis implicated significant effects on metabolic pathways, including the pentose phosphate pathway, histidine metabolism, beta-alanine metabolism, as well as alanine, aspartate, and glutamate metabolism. This comprehensive study unravels the intricate molecular and metabolic responses of D. magna to finasteride exposure, underscoring the multifaceted impacts of this anti-androgenic compound on a keystone species of freshwater ecosystems. The findings emphasize the importance of understanding the environmental repercussions of widely used pharmaceuticals to protect biodiversity in aquatic ecosystems.

Management of Benign Prostatic Hyperplasia in 2024

Benign prostatic hyperplasia (BPH) is a condition involving the proliferation of smooth muscle and epithelial cells within the transition zone of the prostate. The process by which this takes place is not precisely known. It does require that testosterone and 5-alpha reductase convert it to dihydrotestosterone (DHT) which is the active androgen within the prostate. The growth of the prostate results from an imbalance between cell growth and cell death. Obstruction occurs via compression of the urethra by the resulting hyperplastic nodules, as well as increased smooth muscle tone and resistance within the enlarged gland. It is an almost universal process in men beginning in their 40’s; it increases to a prevalence of 60% by age 60 and 80% by age 80.1 This results in progressive bladder outlet obstruction (BOO) and lower urinary tract symptoms (LUTs). Patients can range from being asymptomatic to severely symptomatic. In the most extreme cases, it can result in complete urinary retention and renal dysfunction. The annual economic impact of BPH has been estimated at nearly $4 billion in the Unites States.

Suicide and Intentional Self-harm Among Older Men Treated With 5-Alpha Reductase Inhibitor or Alpha-blockers for Benign Prostatic Hyperplasia

ObjectiveTo compare the risk of intentional self-harm (ISH) and suicide in older men using 5-α reductase inhibitors (5-ARIs) and alpha-blockers for benign prostatic hyperplasia (BPH). Observational research of older men with BPH suggested an increase in ISH with 5-ARI use compared with nonuse; we aimed to address potential confounding by indication with an active comparator reference group. MethodsUsing Medicare data linked to the National Death Index (NDI) from 2007-2016, we implemented a retrospective cohort design in males aged ≥65 years who initiated 5-ARI or alpha-blocker use for BPH. ISH was identified using ICD-9-CM and ICD-10-CM diagnosis codes. Suicides were identified through cause-of-death information from the NDI. We used inverse probability of treatment weighted Cox proportional hazards regression to compare time-to-event between treatment groups, with robust variance estimation. ResultsThe event rates for ISH and suicide, respectively, were 0.314 and 0.308 per 1000 person-years (PY) among 5-ARI users (n=181,675), and 0.364 and 0.382 per 1000PY among alpha-blocker users (n=850,476). For 5-ARI use relative to alpha-blocker use, hazard ratios (HRs) for ISH and suicide, respectively, were 0.88 (95% CI:0.62–1.25) and 0.82 (95% CI:0.54–1.24); for the composite outcome (non-fatal ISH or suicide), the HR was 0.88 (95% CI:0.66–1.16). Subgroup and sensitivity analyses supported these results. Conclusion5-ARI use was not associated with an increased risk for ISH or suicide compared to alpha-blocker use in older men with BPH. Study limitations included low event rates and potentially low sensitivity for ISH events.

5 mC modification of steroid hormone biosynthesis-related genes orchestrates feminization of channel catfish induced by high-temperature

To elucidate the mechanism behind channel catfish feminization induced by high temperature, gonad samples were collected from XY pseudo-females and wild-type females and subjected to high-throughput sequencing for Whole-Genome-Bisulfite-Seq (WGBS) and transcriptome sequencing (RNA-Seq). The analysis revealed 50 differentially methylated genes between wild-type females and XY pseudo-females, identified through the analysis of KEGG pathways and GO enrichment in the promoter of the genome and differentially methylated regions (DMRs). Among these genes, multiple differential methylation sites observed within the srd5a2 gene. Repeatability tests confirmed 7 differential methylation sites in the srd5a2 gene in XY pseudo-females compared to normal males, with 1 specific differential methylation site (16608174) distinguishing XY pseudo-females from normal females. Interestingly, the expression of these genes in the transcriptome showed no difference between wild-type females and XY pseudo-females. Our study concluded that methylation of the srd5a2 gene sequence leads to decreased expression, which inhibits testosterone synthesis while promoting the synthesis of 17β-estradiol from testosterone. This underscores the significance of the srd5a2 gene in the sexual differentiation of channel catfish, as indicated by the ipu00140 KEGG pathway analysis.

A phase II trial of enzalutamide (Enz) with 5-alpha reductase inhibitors (5-ARI) as an androgen deprivation therapy (ADT)–sparing approach for older men with castration-sensitive prostate cancer (CSPC).

A phase II trial of enzalutamide (Enz) with 5-alpha reductase inhibitors (5-ARI) as an androgen deprivation therapy (ADT)–sparing approach for older men with castration-sensitive prostate cancer (CSPC).

Bioprospecting of potential inhibitors of 5alpha reductase 2 inhibitors from relevant ethno-pharmacological plants via in silico techniques

Approximately 60 % of men globally over the age of 50 experience a diminished quality of life as a result of benign prostatic hyperplasia (BPH). Consequently, while the national direct cost for managing BPH is hovering around $4 billion in the USA, the individual direct cost for medications is estimated at $1536 and $425 annually for the USA and Ghana, respectively. Due to the chemotherapeutic drawbacks in BPH treatment, a concerted effort is urgently needed to find new chemotypes with novel mechanism of action to combat the disease. This research aims to employ computational techniques to identify new compounds from ethno-pharmacological plants from Ghana for treating BPH. Altogether, 250 natural products from Croton membranaceus, Heliotropium angiospermum, Annona muricata, Serenoa repens, Cissus quadrangularis, Tribulus terrestrials, Vernonia amagdalina and Momordica foetida from Ghanaian origin were virtually screened against 5alpha reductase 2 (5aR2), a primary drug target implicated in the parthenogenesis of BPH. Out of the 254 compounds docked, three compounds (A, B and C) showed a binding energy lower than testosterone (-10.4 kcal/mol), the main substrate of the target and comparative to finasteride (-11.7 kcal/mol), one of the drugs currently used for treating the disease. Molecular docking and dynamics simulations studies revealed Leu224 to be critical for ligand binding and complex stability. The pharmacological and physicochemical profiles show the compounds to possess good pharmacodynamics with negligible toxicities. While the compounds A, C, G, H, I and J were, respectively, predicted to treat prostate disorders with Pa (0.909, 0.221, 0.743, 0.729, 0.978, and 0.443) and Pi (0.003, 0.132, 0.005,0.005, 0.002, 0.016), that of A, B, D, G, H, I, and J were found to be associated with the inhibition of 5alpha reductase with Pa (0.840, 0.102, 0.097, 0.377, 0.123, 0.909, and 0.201) and Pi (0.001, 0.075, 0.089, 0.003, 0.036, 0.001, and 0.004), respectively. These lead-like compounds possessing plausible chemotherapeutic moieties with putative 5aR2 inhibitory potential need further experimental validation via in vitro studies.

Sex Reassignment Dilemma in 4 Yemeni Siblings with Five Alpha-Reductase Type 2 Deficiency

5α-Reductase two deficiency (5αR2D) is an autosomal recessive 46, XY disorder impacting the HeRD5A2 gene, causing ambiguous genitalia. Four Yemeni siblings with this condition sought guidance from the Sudanese Intersex Working Group (SIWG) in adulthood. A multidisciplinary evaluation was conducted, encompassing physical, mental, hormonal, and imaging examinations, although genetic mutation analysis of the srd5a2 gene was precluded due to limited facilities. Participants were initially assigned as females by an untrained birth attendant; the siblings later manifested virilisation before puberty, prompting a reassignment to the male sex. Despite presenting with 46 XY DSD due to 5αR2D, their sexual identity conflict led them to seek counsel from the SIWG. Comprehensive assessments confirmed the 5αR2D diagnosis. Extensive counselling with the family revealed their resolute decision to maintain the male sex despite concerns highlighted by the SIWG regarding future sexual function and fertility. This case underscores the significant challenges stemming from inadequate knowledge and interventions, emphasising the critical need for early diagnosis, proper genetic counselling, and expert management. Timely referrals to specialised facilities and consideration of options such as in vitro fertilisation (IVF) and preimplantation genetic diagnosis (PGD) for subsequent children are imperative. This report advocates for proactive measures in similar cases, emphasising the importance of tertiary care facilities for accurate diagnosis, informed decision-making, and optimal management of 5αR2D-related dilemmas.

Clinical, Hormonal, and Genetic Spectrum of 46 XY Disorders of Sexual Development (DSD) Patients.

To evaluate the clinical,hormonaland genetic characteristics of 46XY disorders of sexual development (DSD) patients from South India. 46XY DSD patients with a provisional diagnosis of 17β-hydroxysteroid dehydrogenase 3 (17BHSD3) deficiency, 5 alpha-reductase type 2 deficiency (5ARD2) or partial androgen insensitivity syndrome (PAIS) based on clinical and hormonal analysis were included in this study. All the patients underwent detailed clinical and hormonal evaluations. Targeted next-generation sequencing for all three genes (AR, HSD17B3, and SRD5A2) in parallel was carried out for all the included patients and their parents. Based upon the clinical and hormonal analysis, among the 37 children with 46XY DSD in the present study, 21 children were diagnosed with 5ARD2, 10 with PAIS, and six with 17BHSD3 deficiency. However, genetic analysis revealed pathogenic mutations in nine patients - six in the AR gene, two in the SRD5A2 gene, and one in the HSD17B3 gene. The concordance rate between provisional hormonal and genetic diagnosis was only 22.2%. Two out of six subjects with AR gene variants were positive for somatic mosaicism. In the present study, a positive genetic diagnosis was detected in nine patients (24%), including five novel variants. In this study, mutations in the AR gene was the most reported. The authors did not find the testosterone: dihydrotestosterone (T: DHT) ratio to be an accurate hormonal diagnostic tool.

Capsaicin reduces blood glucose and prevents prostate growth by regulating androgen, RAGE/IGF-1/Akt, TGF-β/Smad signalling pathway and reversing epithelial-mesenchymal transition in streptozotocin-induced diabetic mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disease. Diabetes increases the risk of benign prostatic hyperplasia (BPH). Capsaicin is extracted from chili peppers and possesses many pharmacological properties, including anti-diabetic, pain-relieving, and anti-cancer properties. This study aimed to investigate the effects of capsaicin on glucose metabolism and prostate growth in T2DM mice and uncover the related mechanisms. Mice model of diabetes was established by administering a high-fat diet and streptozotocin. Oral administration of capsaicin for 2weeks inhibited prostate growth in testosterone propionate (TP)-treated mice. Furthermore, oral administration of capsaicin (5mg/kg) for 2weeks decreased fasting blood glucose, prostate weight, and prostate index in diabetic and TP-DM mice. Histopathological alterations were measured using hematoxylin & eosin (H&E) staining. The protein expression of 5α-reductase type II, androgen receptor (AR), and prostate-specific antigen (PSA) were upregulated in diabetic and TP-DM mice, but capsaicin reversed these effects. Capsaicin decreased the protein expression of p-AKT, insulin-like growth factor-1 (IGF-1), IGF-1R, and the receptor for advanced glycation end products (RAGE) in diabetic and TP-DM mice. Capsaicin also regulated epithelial-mesenchymal transition (EMT) and modulated the expression of fibrosis-related proteins, including E-cadherin, N-cadherin, vimentin, fibronectin, α-SMA, TGFBR2, TGF-β1, and p-Smad in TP-DM mice. In this study, capsaicin alleviated diabetic prostate growth by attenuating EMT. Mechanistically, capsaicin affected EMT by regulating RAGE/IGF-1/AKT, AR, and TGF-β/Smad signalling pathways. These results provide with new therapeutic approach for treating T2DM or T2DM-induced prostate growth.