Steroids最新文献

{"title":"Evaluation of structural features of anabolic-androgenic steroids: entanglement for organ-specific toxicity","authors":"Ankan Sinha ,&nbsp;Vishal Kumar Deb ,&nbsp;Abhijit Datta ,&nbsp;Satpal Yadav ,&nbsp;Ashish Phulkar ,&nbsp;Suman Adhikari","doi":"10.1016/j.steroids.2024.109518","DOIUrl":"10.1016/j.steroids.2024.109518","url":null,"abstract":"<div><div>Anabolic-androgenic steroids (AASs), more correctly termed “steroidal androgens”, are a broad category of compounds including both synthetic derivatives and endogenously produced androgens like testosterone, which have long been employed as performance-enhancing substances, primarily among recreational athletes and some professionals. While their short-term effects on muscle physiology are well-documented, the long-term health consequences remain inadequately understood. A key finding is the disruption of hormone production, leading to reversible and irreversible changes, particularly with prolonged use. While debate exists over the prevalence of adverse effects, studies suggest a spectrum of somatic and psychiatric consequences, highlighting the need for improved understanding and prevention strategies. AASs are not only affect muscle structure but also influence mood, behavior, and body image, potentially exacerbating substance dependence and psychological distress. Liver alterations are a prominent concern, with oxidative stress implicated in AAS-induced hepatotoxicity. Reproductive complications, including gonadal atrophy and infertility, are common, alongside virilization and feminization effects in both genders. Cardiovascular effects are particularly worrisome, with AASs implicated in hypertension, dyslipidemia, and increased thrombotic risk, contributing to cardiovascular morbidity and mortality. Moreover, AASs may enhance cancer risks, potentially accelerating carcinogenesis in various tissues, including the prostate. The review emphasizes the need for comprehensive public health initiatives to mitigate harm, including harm minimization strategies, routine health screenings, and targeted interventions for AAS users. Understanding the complex interplay of biological mechanisms and systemic effects is crucial for informing clinical management and preventive measures. This review also examines the biological impact of AASs on human muscles, detailing mechanisms of action, chemistry, and associated health risks such as liver damage, cardiovascular disease, and endocrine dysfunction.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109518"},"PeriodicalIF":2.1,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142320080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SPRY4 regulates ERK1/2 phosphorylation to affect oxidative stress and steroidogenesis in polycystic ovary syndrome","authors":"Yu Pan ,&nbsp;Chunxia Yang ,&nbsp;Yan Sun,&nbsp;Shenmin Zhang,&nbsp;Tongmin Xue,&nbsp;Feng Li,&nbsp;Dan Fu","doi":"10.1016/j.steroids.2024.109516","DOIUrl":"10.1016/j.steroids.2024.109516","url":null,"abstract":"<div><div>Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in women of childbearing age. The role of Sprouty RTK Signaling Antagonist 4 (SPRY4) in ovarian function in PCOS was investigated herein, focusing on its regulation of ERK1/2 phosphorylation. PCOS models were established in mice using dehydroepiandrosterone (DHEA). The expression levels of SPRY4 in ovarian tissues were analyzed through RT-qPCR and immunohistochemistry. SPRY4 knockdown was achieved via lentivirus, and its effects on endocrine function, ovarian morphology, oxidative stress, and ERK1/2 phosphorylation were evaluated. Afterwards, granulosa cells were isolated and treated with DHEA and ERK2 agonist <em>tert</em>-Butylhydroquinone. The impacts of ERK2 activation on the regulation of SPRY4 knockdown were assessed using ELISA, fluorescent probes, western blotting, and biochemical assays. SPRY4 knockdown normalized the estrous cycle, reduced serum levels of testosterone, anti-Müllerian hormone, and luteinizing hormone/follicle-stimulating hormone ratio, and improved ovarian morphology. Additionally, SPRY4 knockdown alleviated oxidative stress by decreasing reactive oxygen species and malondialdehyde levels while increasing superoxide dismutase activity. It also restored steroidogenic enzyme expression, which were disrupted by DHEA induction. In vitro, SPRY4 knockdown enhanced granulosa cell viability and reduced ERK1/2 phosphorylation, with <em>tert</em>-Butylhydroquinone reversing these effects and restoring oxidative stress and steroidogenesis disruptions. Together, SPRY4 modulates ERK1/2 phosphorylation to influence oxidative stress and steroidogenesis in PCOS. Targeting SPRY4 may provide novel therapeutic avenues for improving ovarian function and managing PCOS.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109516"},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142308584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Palladium catalysed cross coupling reactions on 2,3-isoxazol-17α-ethynyltestosterone, their anti-cancer activity, molecular docking studies and ADMET analysis","authors":"Astha Yadav ,&nbsp;Anmol Verma ,&nbsp;Saurabh Kumar Singh ,&nbsp;Rohit Prakash ,&nbsp;Sanjay Srivastava ,&nbsp;Arun Sethi ,&nbsp;Ranvijay Pratap Singh","doi":"10.1016/j.steroids.2024.109515","DOIUrl":"10.1016/j.steroids.2024.109515","url":null,"abstract":"<div><div>In the current study, the Sonogashira coupling reaction of danazol with aryl halides was carried out, yielding new aryl substituted danazol derivatives. The synthetic compounds were examined for anti-cancer potential on the HeLa human cervical cancer cell line, and they showed promising cytotoxic action. Synthesized compounds <strong>2</strong>, <strong>4</strong> and <strong>5</strong> inhibited the growth of HeLa cervical cancer cells, potentially making them effective anti-cancer drugs in the future. Furthermore, molecular docking studies were performed to evaluate the inhibitory impact of danazol derivatives on the Human Papillomavirus (HPV) target protein (1F9F). The docking results showed a significant inhibitory action against the cervical cancer protein (1F9F). The binding energy (ΔG) values of <strong>1</strong>, <strong>2</strong>, <strong>3</strong>, <strong>4</strong> and <strong>5</strong> against the protein 1F9F were −<strong>8.01</strong>, <strong>−8.70</strong>, <strong>−9.43</strong>, <strong>−9.58</strong> and <strong>−9.75</strong> kcal/mol, indicating a high affinity of the synthesized compounds to bind with the HPV target proteins compared to their parent compound danazol (<strong>1</strong>). ADMET analyses of all derivatives have also been carried out.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109515"},"PeriodicalIF":2.1,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ergostanes from the mushroom Trametes versicolor and their cancer cell inhibition: In vitro and in silico evaluation","authors":"Alice W. Njue ,&nbsp;Josiah Omolo ,&nbsp;Ryan S. Ramos ,&nbsp;Cleydson B.R. Santos ,&nbsp;Njogu M. Kimani","doi":"10.1016/j.steroids.2024.109511","DOIUrl":"10.1016/j.steroids.2024.109511","url":null,"abstract":"<div><div>In this study, five steroid compounds were isolated from the fruiting bodies mushroom <em>Trametes versicolor.</em> The compounds, 9,19-cyclolanostane-3,29-diol (<strong>3</strong>), ergosta-7,22-dien-3-acetate (<strong>4</strong>), and ergosta-8(14),22-dien-3β,5α,6β,7α-tetrol (<strong>5</strong>), were identified from <em>T. versicolor</em> for the first time. The five compounds were evaluated for their activity against cancer cell lines. Compound 5α,8α–epidioxyergosta-6,22-dien-3β-ol (<strong>1</strong>) was found to be the most effective against most of the cancer cell lines tested. <em>In silico</em> studies showed that compound <strong>1</strong> has good binding affinities to different cancer targets, namely cyclin-dependent kinase 2 (cdk2), human cyclin-dependent kinase 6 (cdk6), Human Topo IIa ATPase/AMP-PNP, anti-apoptotic protein Bcl-2, and Vegfr-2. It’s also druglike based on Lipinski’s rule of five and it’s ADME/Tox properties. Therefore, compound <strong>1</strong> is a good candidate in the management of cancer. These results further show that <em>T. versicolor</em> is a potential source of drugs or drug leads for cancer treatment.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109511"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the influence of estrous cycle-dependent hormonal changes on neurogenesis in adult mice","authors":"Leila Mirzaeian ,&nbsp;Khadijeh Bahrehbar ,&nbsp;Mandana Emamdoust ,&nbsp;Masoumeh Amiri ,&nbsp;Maryam Azari ,&nbsp;Mohammad Taghi Ghorbanian","doi":"10.1016/j.steroids.2024.109513","DOIUrl":"10.1016/j.steroids.2024.109513","url":null,"abstract":"<div><h3>Objective</h3><div>Neurogenesis is the process of generating new neurons from neural stem cells (NSCs) in the adult brain. Sex hormones play an essential role in the development of the brain. The aim of this study was to evaluate the neurogenic changes in the brain at different phases of the estrous cycle in adult mice.</div></div><div><h3>Materials and methods</h3><div>Female NMRI mice were divided into four groups: 1- Estrous, 2- Proestrous, 3- Metestrous, and 4- Diestrous. Different stages of the estrous cycle were determined by staining of vaginal smears. The level of estrogen, progesterone, prolactin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) hormones was evaluated by the enzyme-linked immunosorbent assay (ELISA) method. The expression of brain-derived neurotrophic factor) <em>BDNF</em>)<em>,</em> nerve growth factor (<em>NGF</em>)<em>,</em> ciliary neurotrophic factor<!--> <!-->(<em>CNTF</em>)) genes in hippocampal and the expression of glial fibrillary acidic protein (GFAP) in subventricular zone (SVZ) tissue were evaluated.</div></div><div><h3>Results</h3><div>The serum estrogen and FSH increased significantly in Proestrous group (p &lt; 0.001). Also, progesterone and prolactin hormones were significantly increased in the Diaestrus group (p &lt; 0.001). The expression levels of <em>BDNF</em>, <em>NGF,</em> and <em>CNTF</em> significantly increased in the hippocampal tissue of Proestrous and Diaestrus groups (p &lt; 0.001). The number of GFAP⁺ cells in SVZ of the Proestrous and Diestrous groups had a significant increase (p &lt; 0.05, p &lt; 0.01, p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Our data showed that Changes in sex hormones, especially estrogen in the estrous cycle, can cause the production of new neurons and astrocytes in the hippocampus and SVZ. Therefore, the increase in neurotrophic factors in the Proestrus and Diestrus leads to neurogenesis in adult mice brains.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109513"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142295973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurotoxic mechanisms of dexamethasone in SH-SY5Y neuroblastoma cells: Insights into bioenergetics, oxidative stress, and apoptosis","authors":"Ekramy M. Elmorsy ,&nbsp;Ayat B. Al-Ghafari ,&nbsp;Huda A. Al Doghaither ,&nbsp;Manal S. Fawzy ,&nbsp;Shaimaa A. Shehata","doi":"10.1016/j.steroids.2024.109514","DOIUrl":"10.1016/j.steroids.2024.109514","url":null,"abstract":"<div><p>Despite the known therapeutic uses of dexamethasone (DEX), the specific mechanisms underlying its neurotoxic effects in neuronal cells, particularly in undifferentiated human neuroblastoma (SH-SY5Y) cells, remain inadequately understood. This study aims to elucidate these mechanisms, emphasizing bioenergetics, oxidative stress, and apoptosis, thereby providing novel insights into the cellular vulnerabilities induced by chronic DEX exposure. The findings revealed significant reductions in cell viability, altered membrane integrity with LDH leakage, decreased intracellular ATP production, and the electron transport chain complexes I and III activity inhibition. DEX significantly increased the release of the reactive species and peroxidation of lipids, as well as of Nrf2 expression. At the same time, it simultaneously led to a decline in the activities of the antioxidant catalase and superoxide dismutase enzymes, along with a depletion of glutathione reserves. The apoptosis process was exhibited by a significant elevation of caspases 3 and 8 activities with overexpression of mRNA BAX, inhibition of BCL-2, and a significant upregulation of the BAX/BCL-2 ratio. Assessment of neuronal development genes (<em>GAP43</em>, <em>CAMK2A</em>, <em>CAMK2B</em>, <em>TUBB3</em>, and <em>Wnts</em>) by quantitative PCR assay showed increased expression of <em>CAMK2A</em>, <em>CAMK2B</em>, and <em>Wnt3a</em> with a significant reduction in <em>GAP43</em> mRNA levels. Collectively, this study proved that DEX was cytotoxic to SH-SY5Y via bioenergetic disruption, mitochondrial dysfunction, oxidative stress, and apoptosis.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109514"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142271024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of metabolic and microbial influences on women with polycystic ovarian syndrome","authors":"Foram K. Ravat,&nbsp;Janki R. Goswami,&nbsp;Sneha M. Nair,&nbsp;Kashyap N. Thummar","doi":"10.1016/j.steroids.2024.109512","DOIUrl":"10.1016/j.steroids.2024.109512","url":null,"abstract":"<div><h3>Introduction</h3><p>Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine and metabolic disorder affecting reproductive-aged women worldwide. Characterized by irregular menstruation, signs of hyperandrogenism, polycystic ovaries via ultrasound ovarian dysfunction.</p></div><div><h3>Area covered</h3><p>The review delves into the intricate pathophysiological mechanisms underlying the syndrome. Dysregulation of the hypothalamic-pituitary-ovarian axis, IR, obesity, and hyperandrogenism contribute to anovulation and follicular dysfunction which is associated with gut dysbiosis, bile metabolites, and an unhealthy diet.</p><p>Metabolomics and genomics analyses offer insights into the metabolism of bile acids (BAs) and gut microbiota dysbiosis in PCOS. BAs, crucial for metabolic regulation, are influenced by microbes, impacting hormonal balance. Disruptions in gut microbiota contribute to hormonal dysregulation. Interconnected pathways involving BAs and gut microbiota are pivotal in PCOS. Therapeutic implications include a healthy diet, exercise, and interventions targeting gut microbiota modulation and BAs metabolite to alleviate PCOS symptoms and improve metabolic health.</p></div><div><h3>Conclusion</h3><p>PCOS requires a multifaceted, multidisciplinary approach for effective management, including lifestyle changes, medications, and emerging therapies. Tailored strategies considering individual needs and personalized treatment plans are crucial for successful PCOS management. Despite existing knowledge, comprehensive investigations are needed to bridge research gaps and discern the interconnected pathways linking the development of PCOS and the gut-bile axis which are interconnected with metabolic disorders and the development of PCOS. Gut microbiota and hormonal regulation offer promising avenues for innovative therapeutic strategies aimed at addressing the root causes of PCOS and improving patient outcomes.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"212 ","pages":"Article 109512"},"PeriodicalIF":2.1,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interpretation of immunometric, chromatographic and mass spectrometric data for steroids in diagnosis of endocrine disorders","authors":"John W. Honour","doi":"10.1016/j.steroids.2024.109502","DOIUrl":"10.1016/j.steroids.2024.109502","url":null,"abstract":"<div><p>The analysis of steroids for endocrine disorders is in transition from immunoassay of individual steroids to more specific chromatographic and mass spectrometric methods with simultaneous determination of several steroids. Gas chromatography (GC) and liquid chromatography (LC) coupled with mass spectrometry (MS) offer unrivalled analytical capability for steroid analysis. These specialist techniques were often judged to be valuable only in a research laboratory but this is no longer the case. In a urinary steroid profile up to 30 steroids are identified with concentrations and excretion rates reported in a number of ways. The assays must accommodate the wide range in steroid concentrations in biological fluids from micromolar for dehydroepiandrosterone sulphate (DHEAS) to picomolar for oestradiol and aldosterone. For plasma concentrations, panels of 5–20 steroids are reported. The profile results are complex and interpretation is a real challenge in order to inform clinicians of likely implications. Although artificial intelligence and machine learning will in time generate reports from the analysis this is a way off being adopted into clinical practice. This review offers guidance on current interpretation of the data from steroid determinations in clinical practice. Using this approach more laboratories can use the techniques to answer clinical questions and offer broader interpretation of the results so that the clinician can understand the conclusion for the steroid defect, and can be advised to program further tests if necessary and instigate treatment. The biochemistry is part of the patient workup and a clinician led multidisciplinary team discussion of the results will be required for challenging patients. The laboratory will have to consider cost implications, bearing in mind that staff costs are the highest component. GC–MS and LC-MS/MS analysis of steroids are the choices. Steroid profiling has enormous potential to improve diagnosis of adrenal disorders and should be adopted in more laboratories in favour of the cheap, non-specific immunological methods.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"211 ","pages":"Article 109502"},"PeriodicalIF":2.1,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nandrolone decanoate induced kidney injury through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB pathway: The effect of moderate exercise","authors":"Alireza Shirpoor ,&nbsp;Roya Naderi","doi":"10.1016/j.steroids.2024.109503","DOIUrl":"10.1016/j.steroids.2024.109503","url":null,"abstract":"<div><p>Anabolic-androgenic steroids (AAS) abuse is linked to some abnormalities in several tissues including the kidney. However, the precise molecular mediators involved in AAS-induced kidney disorder remain elusive. The main objective of the present study was to investigate the effect of Nandrolone decanoate on kidney injury alone or in combination with moderate exercise and its related mechanisms. Thirty-two male Wistar rats were subdivided randomly into four groups. control (Con), Nandrolone (10 mg/kg)<!--> <!-->(N), Exercise (Exe), Nandrolone + Exercise (N+Exe).</p></div><div><h3>Results</h3><p>After 6 weeks, nandrolone treatment led to a significant increase in functional parameters such as serum cystatin c, urea, creatinine, albuminuria and Albumin/ creatinine ratio indicating kidney dysfunction. Moreover, nandrolone treatment increased vacuolization, focal inflammation, hemorragia, cast formation fibrosis in the renal tissue of rats. miRNA-146a increased in kidney tissue after nandrolone exposure by using RT-PCR which may be considered ideal<!--> <!-->theranomiRNA<!--> <!-->candidates for diagnosis and treatment.</p><p>Western blotting indicated that IRAK1, TRAF6, TNF-α, NF-κB, iNOS and TGF-β protein expressions were considerably elevated in the kidneys of nandrolone treated rats. Moderate exercise could alleviate the renal dysfunction, histological abnormalities and aforementioned proteins. Our findings suggested that nandrolone consumption can cause damage to kidney tissue probably through miRNA-146a targeting IRAK1 and TRAF6 via activation of the NF-κB and TGF-β pathway. These results provide future lines of research in the identification of theranoMiRNAs related to nandrolone treatment, which can be ameliorated by moderate exercise.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"211 ","pages":"Article 109503"},"PeriodicalIF":2.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural perspectives on the androgen receptor, the elusive shape-shifter","authors":"Madisyn J. Johnson,&nbsp;Elizabeth V. Wasmuth","doi":"10.1016/j.steroids.2024.109501","DOIUrl":"10.1016/j.steroids.2024.109501","url":null,"abstract":"<div><p>The androgen receptor (AR) is a type I nuclear receptor and master transcription factor responsible for development and maintenance of male secondary sex characteristics. Aberrant AR activity is associated with numerous diseases, including prostate cancer, androgen insensitivity syndrome, spinal and bulbar muscular atrophy, and androgenic alopecia. Recent studies have shown that AR adopts numerous conformations that can modulate its ability to bind and transcribe its target DNA substrates, a feature that can be hijacked in the context of cancer. Here, we summarize a series of structural observations describing how this elusive shape-shifter binds to multiple partners, including self-interactions, DNA, and steroid and non-steroidal ligands. We present evidence that AR’s pervasive structural plasticity confers an ability to broadly bind and transcribe numerous ligands in the normal and disease state, and explain the structural basis for adaptive resistance mutations to antiandrogen treatment. These evolutionary features are integral to receptor function, and are commonly lost in androgen insensitivity syndrome, or reinforced in cancer.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"211 ","pages":"Article 109501"},"PeriodicalIF":2.1,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142097828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}