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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology
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作者 Yiyang Qin Wenzhen Zhu +6 位作者 Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua Li Xiao-Jiang Li Su Yang 《Neural Regeneration Research》 SCIE CAS 2025年第9期2655-2666,共12页
Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r... Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy. 展开更多
关键词 androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model NEURODEGENERATION neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor
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Clinical Study on Application of Xinrun Tongluo Method Based on the Theory of Collateral Diseases in Treating Androgenic Baldness of Blood Heat Wind Dryness Syndrome
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作者 Yuanjie XU Guoqiang LIANG 《Agricultural Biotechnology》 CAS 2023年第5期104-107,共4页
[Objectives]To explore the intervention effect of the representative formula of Xinrun Tongluo method,Liangxue Xiaofeng Powder,on the incidence of androgenic alopecia in the syndrome of blood heat and wind dryness.[Me... [Objectives]To explore the intervention effect of the representative formula of Xinrun Tongluo method,Liangxue Xiaofeng Powder,on the incidence of androgenic alopecia in the syndrome of blood heat and wind dryness.[Methods]A total of 72 patients with androgenic alopecia in Suzhou TCM Hospital Affiliated to Nanjing University of Chinese Medicine from October,2022 to June,2023 were randomly divided into a control group(36 cases,treated with Western medicine)and a treatment group(36 cases,treated with Chinese herbal formula+Western medicine).The short-term and long-term efficacy of the two groups of patients was compared.[Results]The hair microscopic signs and short-term and long-term efficacy of the treatment group were significantly better than those of the control group before and after treatment,with a statistically significant difference(P<0.05).[Conclusions]The representative formula of Xinrun Tongluo method is Liangxue Xiaofeng Powder,which has better clinical efficacy as an auxiliary Western medicine in the treatment of androgenic alopecia patients with blood heat and wind dryness syndrome,and is worthy of further promotion and application in clinical practice. 展开更多
关键词 Xinrun Tongluo METHOD androgenic ALOPECIA Syndrome of blood heat and WIND DRYNESS
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The Pathogenesis and Treatment Progress of Androgenic Alopecia
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作者 Huijuan Fan Faqing Huang 《Journal of Biosciences and Medicines》 2024年第6期149-158,共10页
Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and p... Androgenic alopecia, also known as seborrheic alopecia, is the most common hair loss disorder in dermatology clinics, mainly characterized by hair follicle miniaturization and progressive hair loss. The etiology and pathogenesis of androgenic alopecia are not clear, but may be related to heredity and androgen metabolism. Currently, minoxidil and finasteride are the only two drugs approved by the U.S. Food and Drug Administration (FDA) for AGA treatment, other treatments include oral minoxidil, hair transplantation, low energy laser therapy (LLLT), platelet-rich plasma (PRP), Chinese medicine microneedles, and combination therapy. With the development of medicine and science, we have ushered in the era of biologics and targeted therapy. In recent years, a variety of signaling pathways for androgenic alopecia have been found, which may provide a basis for targeted therapy for androgenic alopecia. 展开更多
关键词 androgen Alopecia PATHOGENESIS Gene Expression Signal Transduction Treatment Progress Targeted Therapy
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Androgen signaling inhibits de novo lipogenesis to alleviate lipid deposition in zebrafish
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作者 Jing-Yi Jia Guang-Hui Chen +6 位作者 Ting-Ting Shu Qi-Yong Lou Xia Jin Jiang-Yan He Wu-Han Xiao Gang Zhai Zhan Yin 《Zoological Research》 SCIE CSCD 2024年第2期355-366,共12页
Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully unders... Testosterone is closely associated with lipid metabolism and known to affect body fat composition and muscle mass in males.However,the mechanisms by which testosterone acts on lipid metabolism are not yet fully understood,especially in teleosts.In this study,cyp17a1-/-zebrafish(Danio rerio)exhibited excessive visceral adipose tissue(VAT),lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis(DNL)enzymes.The assay for transposase accessible chromatinwithsequencing(ATAC-seq)results demonstrated that chromatin accessibility of DNL genes was increased in cyp17a1-/-fish compared to cyp17a1+/+male fish,including stearoyl-CoA desaturase(scd)and fatty acid synthase(fasn).Androgen response element(ARE)motifs in the androgen signaling pathway were significantly enriched in cyp17a1+/+male fish but not in cyp17a1-/-fish.Both androgen receptor(ar)-/-and wildtype(WT)zebrafish administered with Ar antagonist flutamide displayed excessive visceral adipose tissue,lipid content,and up-regulated expression and activity of hepatic de novo lipogenesis enzymes.The Ar agonist BMS-564929 reduced the content of VAT and lipid content,and down-regulated acetyl-CoA carboxylase a(acaca),fasn,and scd expression.Mechanistically,the rescue effect of testosterone on cyp17a1-/-fish in terms of phenotypes was abolished when ar was additionally depleted.Collectively,these findings reveal that testosterone inhibits lipid deposition by down-regulating DNL genes via Ar in zebrafish,thus expanding our understanding of the relationship between testosterone and lipid metabolism in teleosts. 展开更多
关键词 Cyp17a1 TESTOSTERONE androgen receptor De novo lipogenesis Fatty acid synthesis
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Quality of Life and Psychological Distress in Women with Mayer-Rokitansky-Küster-Hauser Syndrome and Individuals with Complete Androgen Insensitivity Syndrome
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作者 Kerstin Krupp Maike Fliegner +3 位作者 Franziska Brunner Sara Brucker Katharina Rall Hertha Richter-Appelt 《Open Journal of Medical Psychology》 2014年第3期212-221,共10页
Purpose: This study examines quality of life and psychological distress in individuals with Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS) and Complete Androgen Insensitivity Syndrome (CAIS), two syndromes belon... Purpose: This study examines quality of life and psychological distress in individuals with Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS) and Complete Androgen Insensitivity Syndrome (CAIS), two syndromes belonging to the field of “disorders of sex development”. Methods: Fifty women with MRKHS and eleven individuals with CAIS participated. The German versions of the World Health Organization Quality of Life Questionnaire (short version, WHOQOL-Bref), the Brief Symptom Inventory (BSI), and the Patient Health Questionnaire (PHQ-D) were used as standardized instruments to measure quality of life and psychopathology. Additional questions concerning demographic variables and suicidality were included. Results: In both patient samples examined, general quality of life reported was in the average range (CAIS: mean z-score = ﹣0.43, SD = 1.05;MRKHS: mean z-score = ﹣0.11, SD = 1.06). The standardized instrument assessment revealed increased psychological distress (proportion of clinical cases according to the BSI: CAIS: 54.5%;MRKHS: 55.1%). A correlation between psychological distress and time span from first suspicion to diagnosis was found in women with MRKHS (Spearman’s rho = 0.35, p = 0.018). Conclusions: The results illustrate the importance of individualised and thorough diagnostics when dealing with patients with MRKHS or CAIS. Psychological distress might be an issue for these individuals and therefore should be considered in treatment and counselling. 展开更多
关键词 Mental Health Quality of Life Disorders of SEX Development (DSD) Mayer-Rokitansky-Küster-Hauser SYNDROME (MRKHS) Complete androgen INSENSITIVITY SYNDROME (CAIS)
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Re-Densification Effect of Pressure-Injected Peptide-Hyaluronic Acid Combination on Male Androgenic Alopecia
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作者 Pablo Naranjo 《Journal of Cosmetics, Dermatological Sciences and Applications》 2024年第1期29-44,共16页
Introduction: Mechanism of male androgenic alopecia (MAGA) is complex and leads to an excessive hair shedding and decreased hair density. Oral, topical, and injectable autologous treatments demonstrate ability to stim... Introduction: Mechanism of male androgenic alopecia (MAGA) is complex and leads to an excessive hair shedding and decreased hair density. Oral, topical, and injectable autologous treatments demonstrate ability to stimulate hair re-growth, but the response is suboptimal or plateaus off. Synthetic combination of the peptide complex and hyaluronic acid (P-HA) demonstrated hair regrowth in alopecia patients. Electronically-operated pneumatic injections (EPI) generate micro-trauma in the dermis and under wound-healing conditions may enhance regeneration effect of P-HA. Methods: Subjects seeking improvement of their male pattern hair loss (Hamilton-Norwood type 2-4) received the P-HA treatments through EPI. The course included 4 treatments every two weeks over the 8-week period. In 6 months, the hair growth was assessed comparative to baseline by global clinical photography and digital phototrichograms. The treatment safety and tolerability were documented through the whole study period. Results: Twelve men (30-45 years old) completed the treatment course with high tolerability and without adverse events. Post-treatment assessment of the previously bald areas showed improved coverage on the clinical photographs. The phototrichograms demonstrated statistically significant increase in terminal hair density by 36%, cumulative hair thickness by 37%, and follicular units by 20%;all contributing to a 38% increase in cumulated hair density (all p Conclusion: Electronic pneumatic injections are well tolerated and can be safely used for the needle-free administration of the peptide-hyaluronic acid combination in MAGA therapy. We achieved significant hair re-densification in the balding scalp. The exact role of the EPI-induced impact in the hair re-growth mechanism remains to be ascertained. . 展开更多
关键词 Jet Injections Electronic Pneumatic Injections Male androgenic Alopecia Bioactive Peptides EnerJet
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Characterization of distinct microbiota associated with androgenetic alopecia patients treated and untreated with platelet-rich plasma(PRP)
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作者 Qian Zhang Yanan Wang +5 位作者 Cheng Ran Yingmei Zhou Zigang Zhao Tianhua Xu Hongwei Hou Yuan Lu 《Animal Models and Experimental Medicine》 CAS CSCD 2024年第2期106-113,共8页
Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its r... Background:Androgenic alopecia(AGA)is the most common type of hair loss in men,and there are many studies on the treatment of hair loss by platelet-rich plasma(PRP).The human scalp contains a huge microbiome,but its role in the process of hair loss remains unclear,and the relationship between PRP and the microbiome needs further study.Therefore,the purpose of this study was to investigate the effect of PRP treatment on scalp microbiota composition.Methods:We performed PRP treatment on 14 patients with AGA,observed their clinical efficacy,and collected scalp swab samples before and after treatment.The scalp microflora of AGA patients before and after treatment was characterized by amplifying the V3-V4 region of the 16 s RNA gene and sequencing for bacterial identification.Results:The results showed that PRP was effective in the treatment of AGA patients,and the hair growth increased significantly.The results of relative abundance analysis of microbiota showed that after treatment,g_Cutibacterium increased and g_Staphylococcus decreased,which played a stable role in scalp microbiota.In addition,g_Lawsonella decreased,indicating that the scalp oil production decreased after treatment.Conclusions:The findings suggest that PRP may play a role in treating AGA through scalp microbiome rebalancing. 展开更多
关键词 androgenic alopecia MICROBIOME platelet-rich plasma SCALP
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Exogenous testosterone therapy on choroid in androgen deficiency
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作者 Volkan Yeter Nurullah Koçak +2 位作者 Merve Kalyoncu Ramazan Aşçi Nurşen Aritürk 《International Journal of Ophthalmology(English edition)》 SCIE CAS 2024年第8期1489-1494,共6页
AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers ... AIM:To investigate the effects of exogenous testosterone treatment on the choroidal parameters in patients with androgen deficiency.METHODS:Right eyes of 24 patients with androgen deficiency and 31 healthy volunteers were included in the study.The eyes were scanned for subfoveal choroidal thickness(SFCT),choroidal vascularity index(CVI),choroidstromal area(C-SA),choroid-luminal area(C-LA),choroidstromal to luminal area ratio(CSLR),and the choroidal parameters within central 1500μm of the macula(CVI1500,C-LA1500,C-SA1500,and CSLR1500)by enhanced-depth imaging optical coherence tomography(EDI-OCT)at baseline,6th and 18th weeks of the exogenous testosterone treatment.RESULTS:The mean SFCT values of the androgen deficient groups and healthy controls were 307.7±27.0 and 303.2±37.2μm(P=0.8).However,CVI,C-SA,CSLR,CVI1500,C-LA1500,and CSLR1500 were significantly different between the groups(all P<0.01).At the 6th week visit after exogenous testosterone treatment,SFCT,CVI,C-LA,and C-SA were significantly decreased,and these parameters returned to baseline levels at the 18th-week visit(all P>0.05).However,CVI1500 and LA1500 significantly increased at the end of the follow-up period(P<0.001).CONCLUSION:CVI is lower in androgen-deficient patients than in healthy subjects.The alterations in the choroid during the testosterone peak are transient in the treatment of patients with androgen deficiency.However,the increase in CVI within the central 1500μm of the macula persists even after 4mo. 展开更多
关键词 TESTOSTERONE androgen deficiency CHOROID vascularity index
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Androgen Receptor Promotes Lung Cancer Metastasis by Modifying the miR23a-3p/EPHB2 Pathway
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作者 Yan YANG Jing-wen HUANG Wei-wei YU 《Current Medical Science》 SCIE CAS 2024年第5期954-963,共10页
Objective This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients.Methods Through various techniques,such as Argonaute immunoprecipi... Objective This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients.Methods Through various techniques,such as Argonaute immunoprecipitation,luciferase assays,and ChIP,this study confirmed the positive effects of androgen receptor(AR)on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models.Results The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level,which in turn required changes in miRNA-23a-3p.Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR.Conclusion This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis. 展开更多
关键词 androgen receptor lung cancer metastasis miRNA-23a-3p EPHB2
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Whole exome sequencing and single nucleotide polymorphism array analyses to identify germline alterations in genes associated with testosterone metabolism in a patient with androgen insensitivity syndrome and early-onset colorectal cancer
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作者 Vittoria Disciglio Andrea Devecchi +10 位作者 Orazio Palumbo Massimo Carella Donata Penso Massimo Milione Giorgio Valle Marco Alessandro Pierotti Marco Vitellaro Lucio Bertario Silvana Canevari Stefano Signoroni Loris De Cecco 《Chinese Journal of Cancer》 SCIE CAS CSCD 2016年第10期546-559,共14页
Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been report... Background: Androgen insensitivity syndrome(AIS), a disorder of sexual development in 46, XY individuals, is caused by loss-of-function mutations in the androgen receptor(AR) gene. A variety of tumors have been reported in association with AIS, but no cases with colorectal cancer(CRC) have been described.Case presentation: Here, we present a male patient with AIS who developed multiple early-onset CRCs and his pedigree. His first cousin was diagnosed with AIS and harbored the same AR gene mutation, but with no signs of CRC. The difference in clinical management for the two patients was that testosterone treatment was given to the proband for a much longer time compared with the cousin. The CRC family history was negative, and no germline mutations in well-known CRC-related genes were identified. A single nucleotide polymorphism array revealed a microduplication on chromosome 22q11.22 that encompassed a micro RNA potentially related to CRC pathogenesis. In the proband, whole exome sequencing identified a polymorphism in an oncogene and 13 rare loss-of-function variants, of which two were in CRC-related genes and four were in genes associated with other human cancers.Conclusions: By pathway analysis, all inherited germline genetic events were connected in a unique network whose alteration in the proband, together with continuous testosterone stimulation, may have played a role in CRC pathogenesis. 展开更多
关键词 androgen insensitivity syndrome androgen receptor Colorectal cancer Single nucleotide polymorphism ARRAY TESTOSTERONE Whole EXOME sequencing
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A protein in rat prostatic interacting with androgen regulated gene
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作者 XU YOUHAI, RONG CHANG, QIUPAO SONG AVD SHIMINGCHANGShanghai Institute of Gell Biology, Academia Sinica 《Cell Research》 SCIE CAS CSCD 1991年第1期1-13,共13页
2M NaCl-insoluble fraction of rat ventral prostatechromatin(residual proteins)contain proteins able tointeract specifically with androgen-receptor complex andis,therefore,a part of the acceptor complex.Amongresidual p... 2M NaCl-insoluble fraction of rat ventral prostatechromatin(residual proteins)contain proteins able tointeract specifically with androgen-receptor complex andis,therefore,a part of the acceptor complex.Amongresidual proteins,a 97 KDa protein has been found whichbinds signifieantly to a genomic fragment containingan androgen-regulated gene coding for a 22 KDa protein.The biological significance of this binding in androgenaction need to be further studied. A mini-plasmid clone containing 22 KDa proteincoding sequence was cloned into Charon 4A genomiclibrary from which a 5.7 Kb genomic fragment wasisolated,identified by hybridization with a 5’ and a 3’cDNA probes,and shown to contain the 5’ flankingsequence.Restriction enzyme treatment of this fragmentyielded a 4.7 Kb restriction fragment representingthe 5’ upstream region and a 1.0 Kb containing part ofthe coding sequence.Deletion studies indicated that the97 KDa protein bound only to a subclone of about 300 bpsegment.Furthermore,gel shifting experiment supportedits DNA-prptein binding. 展开更多
关键词 RAT PROSTATIC CHROMATIN 97 KDa residual PROTEIN androgen regulated gene sequences androgen receptor binding sites.
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Androgens and estrogens in skeletal sexual dimorphism 被引量:4
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作者 Michael Laurent Leen Antonio +4 位作者 Mieke Sinnesael Vanessa Dubois Evelien Gielen Frank Classens Dirk Vanderschueren 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第2期213-222,I0008,共11页
Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conver... Bone is an endocrine tissue expressing androgen and estrogen receptors as well as steroid metabolizing enzymes. The bioactivity of circulating sex steroids is modulated by sex hormone-binding globulin and local conversion in bone tissue, for example, from testosterone (T) to estradiol (E2) by aromatase, or to dihydrotestosterone by 5(x-reductase enzymes. Our understanding of the structural basis for gender differences in bone strength has advanced considerably over recent years due to increasing use of (high resolution) peripheral computed tomography. These microarchitectural insights form the basis to understand sex steroid influences on male peak bone mass and turnover in cortical vs trabecular bone. Recent studies using Cre/LoxP technology have further refined our mechanistic insights from global knockout mice into the direct contributions of sex steroids and their respective nuclear receptors in osteoblasts, osteoclasts, osteocytes, and other cells to male osteoporosis. At the same time, these studies have reinforced the notion that androgen and estrogen deficiency have both direct and pleiotropic effects via interaction with, for example, insulin-like growth factor 1, inflammation, oxidative stress, central nervous system control of bone metabolism, adaptation to mechanical loading, etc., This review will summarize recent advances on these issues in the field of sex steroid actions in male bone homeostasis. 展开更多
关键词 androgen receptor bone mineral density ESTRADIOL estrogen receptor male OSTEOBLAST OSTEOCLAST OSTEOCYTE osteoporosis sex hormone-binding globulin testosterone
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Androgen effects on skeletal muscle: implications for the development and management of frailty 被引量:2
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作者 Matthew DL O'Connell Frederick CW Wu 《Asian Journal of Andrology》 SCIE CAS CSCD 2014年第2期203-212,I0007,I0008,共12页
Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in dev... Androgens have potent anabolic effects on skeletal muscle and decline with age in parallel to losses in muscle mass and strength. This loss of muscle mass and function, known as sarcopenia, is the central event in development of frailty, the vulnerable health status that presages adverse outcomes and rapid functional decline in older adults. The potential role of falling androgen levels in the development of frailty and their utility as function promoting therapies in older men has therefore attracted considerable attention. This review summarizes current concepts and definitions in muscle ageing, sarcopenia and frailty, and evaluates recent developments in the study of androgens and frailty. Current evidence from observational and interventional studies strongly supports an effect of androgens on muscle mass in ageing men, but effects on muscle strength and particularly physical function have been less clear. Androgen treatment has been generally well-tolerated in studies of older men, but concerns remain over higher dose treatments and use in populations with high cardiovascular risk. The first trials of selective androgen receptor modulators (SARMs) suggest similar effects on muscle mass and function to traditional androgen therapies in older adults. Important future directions include the use of these agents in combination with exercise training to promote functional ability across different populations of older adults, as well as more focus on the relationships between concurrent changes in hormone levels, body composition and physical function in observational studies. 展开更多
关键词 ageing androgenS body composition FRAILTY muscle physical function SARCOPENIA selective androgen receptor modulators sex hormones TESTOSTERONE
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Influence of Glyphaea brevis twig extract on nucleus, tight junctions and expression of inhibin-β, stem cell factor, and androgen binding protein in TM4 Sertoli cells
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作者 Janet Olayemi Olugbodi Oladipupo David +1 位作者 Oluwafemi Adeleke Ojo Afolabi Clement Akinmoladun 《Asian pacific Journal of Reproduction》 2019年第4期157-166,共10页
Objective: To examine the influence of Glyphaea (G.) brevis twig extract on the mitochondrial dehydrogenase activity, integrity of the tight junctions between adjacent cells, mitochondria, apoptosis, nucleus and expre... Objective: To examine the influence of Glyphaea (G.) brevis twig extract on the mitochondrial dehydrogenase activity, integrity of the tight junctions between adjacent cells, mitochondria, apoptosis, nucleus and expression of inhibin-β, stem cell factor, and androgen binding protein in TM4 Sertoli cells. Methods: TM4 cell line was used in this study as it exhibited properties similar to the Sertoli cells. TM4 Sertoli cells were exposed to G. brevis twig extract (0.1, 1.0, 10.0, 100.0, or 1000.0μg/mL) for 24, 48 and 72 h. Parameters studied included cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay], mitochondrial membrane potential (tetra methyl rhodamine ethyl ester dye), transepithelial electrical resistance, apoptosis (Annexin V Alexa Fluor?488/propidium iodide assay) and mRNA expression (quantitative reverse transcription polymerase chain reaction). Results: G. brevis twig extract had no cytotoxic impact on cell viability, thus, considerably increasing the activity of mitochondrial dehydrogenase enzyme after 24 and 72 h exposure. Transepithelial electrical resistance values revealed substantial (P<0.05) rise in treated groups, especially after 72 h of treatment. Moreover, there was a significant decrease in mitochondrial depolarization of TM4 Sertoli cells exposed to G. brevis twig extract when compared to controls. In addition, G. brevis twig extract significantly reduced necrosis and apoptosis of TM4 Sertoli cells when compared to control. Nevertheless, fluorescence microscopy revealed that the nuclei were egg-shaped and marked uniformly with consistent cell shape at the middle of the TM4 Sertoli cells. Significant stimulatory effects were observed on mRNA levels of inhibin-β, androgen binding protein and stem cell factor. Conclusions: G. brevis twig extract may increase the secretory roles of TM4 Sertoli cells, cells proliferation, as well as cell-cell tight junction integrity. Thus, G. brevis twig may enhance spermatogenesis. 展开更多
关键词 Glyphaea brevis TWIG TM4 SERTOLI cell line Inhibin-β androgen binding protein
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Targeting of Androgen Receptor Expression by Andro-miRs as Novel Adjunctive Therapeutics in Prostate Cancer
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作者 Jey Sabith Ebron Crystal M. Weyman Girish C. Shukla 《Journal of Cancer Therapy》 2013年第4期47-58,共12页
Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant pros... Prostate cancer begins as an androgen-responsive disease. However, subsequent accumulation of multiple sequential genetic and epigenetic alterations transforms the disease into an aggressive, castration-resistant prostate cancer (CRPC). The monoallelic Androgen Receptor (AR) is associated with the onset, growth and development of Prostate cancer. The AR is a ligand-dependent transcription factor, and the targeting of androgen- and AR-signaling axis remains the primary therapeutic option for Prostate cancer (PCa) treatment. A durable and functional disruption of AR signaling pathways combining both traditional and novel therapeutics is likely to provide better treatment options for CRPC. Recent work has indicated that expression of AR is modulated at the posttranscriptional level by regulatory miRNAs. Due to a relatively long 3’ untranslated region (UTR) of AR mRNA, the posttranscription expression is likely to be regulated by hundreds of miRNAs in normal as well as in disease state. The main objective of the article is to offer a thought-provoking concept of “andro-miRs” and their potential application in AR gene expression targeting. This new paradigm for targeting constitutively active AR and its tumor specific splicing isoforms using andro-miRs may pave the way for a novel adjunctive therapy and improved treatment of CRPC. 展开更多
关键词 androgen Receptor microRNA 3 Untranslated Region PROSTATE CANCER CASTRATION-RESISTANT PROSTATE CANCER (CRPC) Andro-miR
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Posttranslational regulation of androgen dependent and independent androgen receptor activities in prostate cancer 被引量:5
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作者 Simeng Wen Yuanjie Niu Haojie Huang 《Asian Journal of Urology》 CSCD 2020年第3期203-218,共16页
Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard t... Prostate cancer(PCa)is the most commonly diagnosed cancer among men in western countries.Androgen receptor(AR)signaling plays key roles in the development of PCa.Androgen deprivation therapy(ADT)remains the standard therapy for advanced PCa.In addition to its ligand androgen,accumulating evidence indicates that posttranscriptional modification is another important mechanism to regulate AR activities during the progression of PCa,especially in castration resistant prostate cancer(CRPC).To date,a number of posttranscriptional modifications of AR have been identified,including phosphorylation(e.g.by CDK1),acetylation(e.g.by p300 and recognized by BRD4),methylation(e.g.by EZH2),ubiquitination(e.g.by SPOP),and SUMOylation(e.g.by PIAS1).These modifications are essential for the maintenance of protein stability,nuclear localization and transcriptional activity of AR.This review summarizes posttranslational modifications that influence androgen-dependent and-independent activities of AR,PCa progression and therapy resistance.We further emphasize that in addition to androgen,posttranslational modification is another important way to regulate AR activity,suggesting that targeting AR posttranslational modifications,such as proteolysis targeting chimeras(PROTACs)of AR,represents a potential and promising alternate for effective treatment of CRPC.Potential areas to be investigated in the future in the field of AR posttranslational modifications are also discussed. 展开更多
关键词 androgen receptor Posttranslational modification Phosphorylation ACETYLATION METHYLATION UBIQUITINATION SUMOYLATION PROTAC SPOP Prostate cancer
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Defective Expression of the Gap Junction Protein Pannexin-1 Channel Contributes to the Formation of PCOS-Realted Androgenetic Alopecia
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作者 Sule Gencoglu Fatma Tanilir Cagiran Zercan Kali 《Advances in Reproductive Sciences》 2023年第4期86-92,共7页
Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS wh... Objective: To determine serum pannexin-1 channel levels and their association with hair loss in women with PCOS diagnosed with female androgenetic alopecia (FAGA). Materials and Methods: Thirty-five women with PCOS who presented with diffuse and treatment-resistant progressive hair loss and were diagnosed with FAGA were included in the study. 25 patients who were diagnosed with female androgenetic alopecia but did not have PCOS were considered as the control group. PCOS and control groups were matched by age. Follicular miniaturization, displacement of terminal hairs with vellus hairs, and a diffuse decrease in hair density were accepted as FAGA in the trcihoscopy examination of the vertex and bitempoaral area. On the third day of the menstrual cycle serum FSH, LH, testosterone, PRL and insulin levels were measured. Insulin resistance was calculated with HOMA-IR. Serum pannexin-1 channel levels of each group were mesured with ELISA. Results: Serum pannexin 1 channels levels of FAGA group due to PCOS were found to be significantly higher than FAGA patients in the control group (2.72 ± 1.09 ng/mL vs 1.65 ± 0.97 ng/mL, p < 0.01). Serum LH, insulin and testosterone levels of PCOS group were significantly higher than controls. HOMA-IR values were significantly higher and >2.5 in the PCOS group compared to the controls. PRL values were similar except for one patient with elevated PRL. Serum FSH values were the same in both groups. A positive and significant correlation was found between pannexin 1 channels levels and HOMA-IR and serum testosterone levels (r = 0.650, p Conclusions: In addition to hyperandrogenemia, increased pannexin 1 channel levels may play a role in the etiology of PCOS associated FAGA, as it impairs the communication between the skin and hair follicle. 展开更多
关键词 androgenetic Alopecia PCOS androgen Pannexin-1 Channel Inflammation
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Primary molecular basis of androgenic gland endocrine sex regulation revealed by transcriptome analysis in Eriocheir sinensis
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作者 SONG Chengwen LIU Lei +3 位作者 HUI Min LIU Yuan LIU Hourong CUI Zhaoxia 《Journal of Oceanology and Limnology》 SCIE CAS CSCD 2019年第1期223-234,共12页
In crustaceans, the male sexual dif ferentiation and maintenance are specially regulated by androgenic gland(AG). However, little is known about the genes involved in the regulation process.RNA-Seq was performed on AG... In crustaceans, the male sexual dif ferentiation and maintenance are specially regulated by androgenic gland(AG). However, little is known about the genes involved in the regulation process.RNA-Seq was performed on AG with ejaculatory duct(AG_ED) and ejaculatory duct(ED) as control in Eriocheir sinensis, one of the most important economic and ?shery crabs with typically sex dimorphism. A total of 925 unigenes were identi?ed as dif ferentially expressed genes(DEGs) and the expression of nine genes randomly selected was con?rmed by qRT-PCR. 667 unigenes were up-regulated in AG_ED, being supposed to be AG preferential genes. Among them, the full length of i nsulin-like androgenic gland factor( IAG) cDNA named as Es-IAG was obtained as a logo gene of AG, which together with the genes i nsulin-like receptor( INR), and s ingle insulin binding domain protein( SIBD), might constitute the sex regulation pathway. Several sex related genes were identi?ed, and their function will have to be investigated. Also,the identi?cation of j uvenile hormone epoxide hydrolase 1( JHEH1), ecdysteroid 22-hydroxylase( DIB) and e cdysone receptor( ECR) preliminarily clari?ed the molecular regulation mechanism of eyestalk-AG-testis axis, which plays important roles in molting and reproduction. The results will enhance our understanding for the molecular basis of the AG involved in male sex regulation in crabs. 展开更多
关键词 androgenic GLAND comparative transcriptome ERIOCHEIR sinensis INSULIN-LIKE androgenic GLAND factor(IAG) SEX REGULATION
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Muscle function, physical performance and body composition changes in men with prostate cancer undergoing androgen deprivation therapy 被引量:8
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作者 Thomas W Storet Renee Miciek Thomas G Travison 《Asian Journal of Andrology》 SCIE CAS CSCD 2012年第2期204-221,共18页
Prostate cancer (PCa) is the most common visceral malignancy in men with androgen deprivation therapy (ADT) the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectivene... Prostate cancer (PCa) is the most common visceral malignancy in men with androgen deprivation therapy (ADT) the preferred therapy to suppress testosterone production and hence tumor growth. Despite its effectiveness in lowering testosterone, ADT is associated with side effects including loss of muscle mass, diminished muscle strength, decrements in physical performance, earlier fatigue and declining quality of life. This review reports a survey of the literature with a focus on changes in muscle strength, physical function and body composition, due to short-term and long-term ADT. Studies in these areas are sparse, especially well-controlled, prospective randomized trials. Cross-sectional and longitudinal data (up to 2 years) for men with PCa treated with ADT as well as patients with PCa not receiving ADT and age-matched healthy men are presented when available. Based on limited longitudinal data, the adverse effects of ADT on muscle function, physical performance and body composition occur shortly after the onset of ADT and tend to persist and worsen over time. Exercise training is a safe and effective intervention for mitigating these changes and initial guidelines for exercise program design for men with PCa have been published by the American College of Sports Medicine. Disparities in study duration, types of studies and other patient-specific variables such as time since diagnosis, cancer stage and comorbidities may all affect an understanding of the influence of ADT on health, physical performance and mortality. 展开更多
关键词 androgen deprivation therapy androgen suppression exercise prescription exercise training functional assessment lean body mass older men prostate cancer
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In situ hybridization assay of androgen receptor gene in hepatocarcinogenesis 被引量:7
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作者 ZHAO Guo Qiang, XUE Ling, XU Hong Yu, TANG Xi Ming, HU Rui De and DONG Jun 《World Journal of Gastroenterology》 SCIE CAS CSCD 1998年第6期48-50,共3页
AIM To determine the correlation between expression of androgen receptor (AR) gene and hepatocarcinogenesis. METHODS Male SD rats were used as experimental animals and the animal model of experimental hepatocarcino... AIM To determine the correlation between expression of androgen receptor (AR) gene and hepatocarcinogenesis. METHODS Male SD rats were used as experimental animals and the animal model of experimental hepatocarcinoma was established by means of 3′ me DAB administration. Androgen receptor mRNA was detected by a non radioactive in situ hybridization assay in neoplastic and non neoplastic liver tissues. RESULTS The expression of androgen receptor mRNA was observed only in neoplastic cells and some atypical hyperplastic cells. In the liver tissue of control animal and the remaining normal liver cells adjacent to the carcinoma tissue, no positive signal was seen. CONCLUSION Androgen has an important correlation with hepatocarcinogenesis and the expression of androgen receptor gene might be a mark event during hepatocarcinogenesis. 展开更多
关键词 HEPATOCARCINOMA androgen RECEPTOR in SITU HYBRIDIZATION liver neoplasm experimental
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