Testicular descent occurs in two consecutive stages:the transabdominal stage and the inguinoscrotal stage.Androgens play a crucial role in the second stage by influencing the development of the gubernaculum,a structur...Testicular descent occurs in two consecutive stages:the transabdominal stage and the inguinoscrotal stage.Androgens play a crucial role in the second stage by influencing the development of the gubernaculum,a structure that pulls the testis into the scrotum.However,the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated.To identify the androgen-regulated genes,we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout(Lhcgr KO)mice,an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency.We found that the expression of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 1(Smoc1)was the most severely suppressed at both the transcript and protein levels,while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice.The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist,flutamide.In addition,in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells.In the cultures of myogenic differentiation medium,both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7(Pax7)and myogenic factor 5(Myf5).After short-interfering RNA-mediated knocking down of Smoc1,the expression of Pax7 and Myf5 diminished,and testosterone alone did not recover,but additional SMOC1 did.These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.展开更多
Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR)gene, has traditionally been examined within the framework of disorders of sex development. However, grow...Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR)gene, has traditionally been examined within the framework of disorders of sex development. However, growingevidence indicates that AR dysfunction also disrupts systemic metabolic homeostasis, predisposing affectedindividuals to insulin resistance and type 2 diabetes mellitus. This article synthesizes recent advances in genetics,transcriptomics, and physiology to elucidate how AR mutations drive tissue-specific metabolic reprogramming inkey organs, including pancreatic β-cells, skeletal muscle, liver, and adipose tissue. Particular attention is given to anewly identified familial AR variant (c.2117A>G;p.Asn706Ser), which not only broadens the known mutationalspectrum of AIS but also underscores the clinical importance of early metabolic risk screening in this population.We further examine how pubertal stage, hormone replacement therapy, and sex-specific signaling pathwaysinteract to influence long-term metabolic outcomes. Lastly, we propose an integrative management framework thatincorporates genetic diagnosis, endocrine surveillance, and personalized pharmacological strategies aimed atreducing the risk of type 2 diabetes mellitus and cardiometabolic complications in individuals with AIS. Distinctfrom previous AIS-centered reviews, this work integrates metabolic and endocrine perspectives into the traditionaldevelopmental paradigm, offering a more comprehensive understanding of disease risk and translational management.展开更多
Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most...Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.展开更多
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
Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was cond...Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.展开更多
The heterogeneity of triple-negative breast cancer(TNBC)has spurred the exploration of precision therapies based on molecular subtypes,with the androgen receptor(AR)-positive subtype emerging as a potential therapeuti...The heterogeneity of triple-negative breast cancer(TNBC)has spurred the exploration of precision therapies based on molecular subtypes,with the androgen receptor(AR)-positive subtype emerging as a potential therapeutic target.The treatment of AR-positive TNBC relies primarily on androgen receptor antagonists,such as enobosarm,bicalutamide,and enzalutamide.To enhance efficacy,researchers are investigating combination therapies that integrate anti-androgen agents with chemotherapy,immunotherapy,or PARP inhibitors.Additionally,studies have revealed that the AR signaling pathway regulates the tumor microenvironment,and AR inhibition may potentiate the efficacy of immune checkpoint inhibitors.However,anti-AR therapies face significant limitations and challenges due to multifaceted factors,necessitating further resolution.With continued advancements,AR-targeted therapy holds promise as a critical component of personalized treatment strategies for TNBC.展开更多
BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen depr...BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.展开更多
Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate...Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.展开更多
Background:Intermediate-risk prostate cancer(IR-PC)represents a heterogeneous group requiring nuanced treatment approaches,and recent advancements in radiotherapy(RT),androgen deprivation therapy(ADT),and prostatespec...Background:Intermediate-risk prostate cancer(IR-PC)represents a heterogeneous group requiring nuanced treatment approaches,and recent advancements in radiotherapy(RT),androgen deprivation therapy(ADT),and prostatespecific membrane antigen positron emission tomography(PSMA-PET/CT)imaging have prompted growing interest in personalized,risk-adapted management strategies.This study by the Turkish Society for Radiation Oncology aims to examine radiation oncologists’practices in managing IR-PC,focusing on RT and imaging modalities to identify trends for personalized treatments.Methods:A cross-sectional survey was conducted among Turkish radiation oncologists treating at least 50 prostate cancer(PC)cases annually.The 22-item questionnaire covered IR-PC management aspects such as risk stratification,imaging preferences,androgen deprivation therapy(ADT)use and duration,RT techniques,and treatment combinations.Anonymous responses were analyzed using descriptive statistics.Results:Thirty radiation oncologists participated,57%with over 20 years of experience.The median annual number of PC cases treated was 130.For risk stratification,43% followed the National Comprehensive Cancer Network(NCCN)guidelines,while 30%used the D’Amico classification.Imaging preferences revealed 47% favored PSMA-PET/CT.External beam RT was universally preferred,with 60% adopting ultra-hypofractionation.ADT was used by 97%,with 73% recommending it for unfavorable IR-PC cases.Short-term ADT(4–6 months)was the standard,administered concurrently with RT by 57%.Cardiovascular status influenced decisions for 97% of respondents,while 37% also considered patient age,preferences,and sexual health.Conclusions:This national survey demonstrates a shift toward personalized care in intermediate-risk prostate cancer in Turkey,marked by selective PSMA-PET/CT use,tailored ADT,and evolving radiotherapy practices.The findings underscore the importance of multidisciplinary collaboration—particularly between urologists and radiation oncologists—to optimize imaging integration and treatment outcomes.展开更多
The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse mod...The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.展开更多
Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resul...Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.展开更多
Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAI...Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.展开更多
Aim: To study the effect of androgen and antiandrogen on the level of androgen receptor (AR) mRNA. Methods: The total RNA was extracted from the prostate and analyzed by slot blot analysis. The blots were hybridized w...Aim: To study the effect of androgen and antiandrogen on the level of androgen receptor (AR) mRNA. Methods: The total RNA was extracted from the prostate and analyzed by slot blot analysis. The blots were hybridized with AR cDNA probe and 1A probe (internal control) and autoradiography was performed. The intensity of signal was measured with a densitometer and the ratio of AR RNA and 1A RNA was calculated. Results: Androgenic deprivation produced by castration decreased the weight of the prostate and increased the levels of AR mRNA. Treatment of the castrated rats with testostrone increased the weight of prostate and decreased the levels of AR mRNA. Treatment of normal rats with flutamide decreased the weight of the gland and increased the levels Of AR mRNA. Conclusion: Androgens produce proliferative effect on the prostate and negatively regulate the AR transcription.展开更多
Aim： To characterize the matrix metalloproteinases （MMP）-2 promoter and to identify androgen response elements （AREs） involved in androgen-induced MMP-2 expression. Methods： MMP-2 mRNA levels was determined by r...Aim： To characterize the matrix metalloproteinases （MMP）-2 promoter and to identify androgen response elements （AREs） involved in androgen-induced MMP-2 expression. Methods： MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction （RT-PCR）. MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays （EMSA） were used to verify the identified AREs in the MMP-2 promoter. Results： Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 （relative to the start codon） of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5＇-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor （AR） interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion： Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.展开更多
Serum testosterone does not correlate with androgen tissue activity, and it is critical to optimize tools to evaluate such activity in males. Ultrasound measurement of bulbocavernosus muscle （BCM） was used to assess...Serum testosterone does not correlate with androgen tissue activity, and it is critical to optimize tools to evaluate such activity in males. Ultrasound measurement of bulbocavernosus muscle （BCM） was used to assess the relationship between the number of CAG repeats （CAGn） in the androgen receptor （AR） and the BCM size; the changes in the number of CAGn over age were also evaluated. Transperineal ultrasound measurement of the BCM was also performed. AR CAGn were determined by high performance liquid chromatography, and morning hormone levels were determined using immunoassays. Forty-eight men had CAG repeat analysis. Twenty-five were 〈30 years of age, mean 23.7 years （s.d, = 3.24） and 23 were 〉45 years of age, mean 53years （s.d. = 5.58）. The median CAGn was 21 （13-29）. BCM area was greater when the number of CAGn were 〈18 as compared to the number of CAGn 〉24 （P= 0.04）. There was a linear correlation between the number of CAGn and the BCM area R^2= 16% （P= 0.01）. In the 45 to 65-years-old group, a much stronger negative correlation （R^2 = 29%, P= 0.01） was noticed. In the 19 to 29-years-old group, no such correlation was found （R2 = 4%, P = 0.36）. In older men, the number of CAGn increased with age （R^2 = 32%, P= 0.01）. The number of CAGn in the AR correlates with the area of the BCM. Ultrasound assessment of the BCM is an effective surrogate to evaluate end-organ activity of androgens. The number of CAGn may increase with age.展开更多
Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do...Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins （HDL） cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.展开更多
Benign prostatic hyperplasia(BPH)is a common urological condition in aging men.High levels of androgens,including testosterone(T)and dihydrotestosterone(DHT),are closely associated with BPH occurrence and development....Benign prostatic hyperplasia(BPH)is a common urological condition in aging men.High levels of androgens,including testosterone(T)and dihydrotestosterone(DHT),are closely associated with BPH occurrence and development.Currently,the main clinical drugs used for BPH treatment are 5α-reductase inhibitors andα-receptor blockers,both of which aim to decrease abnormal androgenic signaling while having several unignored side effects.Recently,various natural herbs,such as tonifying yang traditional Chinese medicine(TCM),have been found to have androgenic activities,some of which are also effective for BPH treatment.Here,we review the androgenic activities of phytoandrogens,together with their therapeutic effects in BPH,and summarize the mechanisms involved,providing evidence that such herbs serve as selective androgen receptor modulators.展开更多
Objective To investigate the androgen receptor （AR） mRNA expression in pancreas, hypothalamus and ovary of androgen sterilized rats （ASR）.Methods ASR model was established by subcutaneous injection of testosterone...Objective To investigate the androgen receptor （AR） mRNA expression in pancreas, hypothalamus and ovary of androgen sterilized rats （ASR）.Methods ASR model was established by subcutaneous injection of testosterone propionate to SD female rats at the age of 9 days. Around the age of 106 days （proestrus）, all rats were killed, serum Δ4-andronestedione （Δ 4-A）, total testosterone （TT）, free testosterone （FT）, insulin （Ins） and C-peptide （C-P） were measured by radioimmunoassay （RIA）. Total RNA in pancreas, hypothalamus and ovary were extracted and the amount of AR mRNA was quantitatedly analyzed by RT-PCR with single base mutant template as inner standard. Results Serum concentrations of Δ4-A, TT, FT, Ins and C-P in ASR model rats were significantly higher than those in control group （P〈0.05, P〈0.01）. The expression of AR mRNA in pancreas, hypothalamus and ovary increased significantly （P〈0. 05, P〈0.01） of model rats as compared with control group. Conclusion The elevated serum androgen levels in ASR model could enhance the expression of AR mRNA levels in pancreas, hypothalamus and ovary, which further induce hyperinsulinemia and anovulation.展开更多
Objective To observe the clinical efficacy of catgut embedment combined with moxibustion and bloodletting in the treatment of androgenic alopecia and to probe into its therapeutic mechanism. Methods Eighty-four patien...Objective To observe the clinical efficacy of catgut embedment combined with moxibustion and bloodletting in the treatment of androgenic alopecia and to probe into its therapeutic mechanism. Methods Eighty-four patients with androgenic alopecia were divided into catgut embedment group （group A） and western medicine group （group B） on the basis of random number table and according to the order of treatment. For the pateints in group A, Shenguan （肾关） on both sides, Minghuang （明黄） and Zusanli （足三里 ST 36） were selected to receive catgut embedment therapy, once every month, combined with moxibustion on the lower abdomen and local bloodletting treatment. For the patients in group B, finasteride 1mg/d was orally administrated. The treatment period for two groups was 3 months, and the follow-up visit lasted for 3 months. Serum testosterone （T） and estradiol （E2） contents were detected respectively before treatment, after i month and 3 months of treatment and after 3 months of follow-up visit, and the specific values were calculated to make statistical analysis of T, E2, T/E2 and curative effects of the two groups after i month and 3 months of treatment and after 3 months of follow-up visit. Results There was no statistical significance in curative effect between the two groups after i month of treatment （P〉0.05）, and the curative effect in group A were better than that in group B after 3 months of treatment or after 3 months of follow-up visit （both P〈0.05）; E2 level in group A was lower than that in group A after 3 months of treatment （P〈0.05）; T, E2 and T/E2 in group A were all lower than that in group B after 3 month of follow-up visit （all P〈0.05）. Conclusion The curative effect of treating androgenic alopecia with catgut embedment, moxibustion and bloodletting is definite, and its mechanism of action may be related to the reduction of T levels and T/E2 values.展开更多
Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject ...Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.展开更多
基金supported in part by the Department of OB/GYN research funds(University of Louisville,Louisville,KY,USA)Jilin Province Health Technology Capability Enhancement funds(No.2022JC055).
文摘Testicular descent occurs in two consecutive stages:the transabdominal stage and the inguinoscrotal stage.Androgens play a crucial role in the second stage by influencing the development of the gubernaculum,a structure that pulls the testis into the scrotum.However,the mechanisms of androgen actions underlying many of the processes associated with gubernaculum development have not been fully elucidated.To identify the androgen-regulated genes,we conducted large-scale gene expression analyses on the gubernaculum harvested from luteinizing hormone/choriogonadotropin receptor knockout(Lhcgr KO)mice,an animal model of inguinoscrotal testis maldescent resulting from androgen deficiency.We found that the expression of secreted protein acidic and rich in cysteine(SPARC)-related modular calcium binding 1(Smoc1)was the most severely suppressed at both the transcript and protein levels,while its expression was the most dramatically induced by testosterone administration in the gubernacula of Lhcgr KO mice.The upregulation of Smoc1 expression by testosterone was curtailed by the addition of an androgen receptor antagonist,flutamide.In addition,in vitro studies demonstrated that SMOC1 modestly but significantly promoted the proliferation of gubernacular cells.In the cultures of myogenic differentiation medium,both testosterone and SMOC1 enhanced the expression of myogenic regulatory factors such as paired box 7(Pax7)and myogenic factor 5(Myf5).After short-interfering RNA-mediated knocking down of Smoc1,the expression of Pax7 and Myf5 diminished,and testosterone alone did not recover,but additional SMOC1 did.These observations indicate that SMOC1 is pivotal in mediating androgen action to regulate gubernaculum development during inguinoscrotal testicular descent.
基金Supported by the Quzhou Science and Technology Plan Project,No.2022K69.
文摘Familial androgen insensitivity syndrome (AIS), resulting from inherited mutations in the androgen receptor (AR)gene, has traditionally been examined within the framework of disorders of sex development. However, growingevidence indicates that AR dysfunction also disrupts systemic metabolic homeostasis, predisposing affectedindividuals to insulin resistance and type 2 diabetes mellitus. This article synthesizes recent advances in genetics,transcriptomics, and physiology to elucidate how AR mutations drive tissue-specific metabolic reprogramming inkey organs, including pancreatic β-cells, skeletal muscle, liver, and adipose tissue. Particular attention is given to anewly identified familial AR variant (c.2117A>G;p.Asn706Ser), which not only broadens the known mutationalspectrum of AIS but also underscores the clinical importance of early metabolic risk screening in this population.We further examine how pubertal stage, hormone replacement therapy, and sex-specific signaling pathwaysinteract to influence long-term metabolic outcomes. Lastly, we propose an integrative management framework thatincorporates genetic diagnosis, endocrine surveillance, and personalized pharmacological strategies aimed atreducing the risk of type 2 diabetes mellitus and cardiometabolic complications in individuals with AIS. Distinctfrom previous AIS-centered reviews, this work integrates metabolic and endocrine perspectives into the traditionaldevelopmental paradigm, offering a more comprehensive understanding of disease risk and translational management.
基金supported in part by DOD Idea Development Award(HT9425-23-1-0295)NIH grants(R01 CA265897 and R21 CA280467)by the Department of Urology,University of Pittsburgh School of Medicine,Pittsburgh,PA,USA。
文摘Androgens play an important role in prostate cancer development and progression.Androgen action is mediated through the androgen receptor(AR),a ligand-dependent DNA-binding transcription factor.AR is arguably the most important target for prostate cancer treatment.Current USA Food and Drug Administration(FDA)-approved AR inhibitors target the ligand-binding domain(LBD)and have exhibited efficacy in prostate cancer patients,particularly when used in combination with androgen deprivation therapy.Unfortunately,patients treated with the currently approved AR-targeting agents develop resistance and relapse with castration-resistant prostate cancer(CRPC).The major mechanism leading to CRPC involves reactivation of AR signaling mainly through AR gene amplification,mutation,and/or splice variants.To effectively inhibit the reactivated AR signaling,new approaches to target AR are being actively explored.These new approaches include novel small molecule inhibitors targeting various domains of AR and agents that can degrade AR.The present review provides a summary of the existing FDA-approved AR antagonists and the current development of some of the AR targeting agents.
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘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.
文摘Objective To evaluate the association of GGN repeat polymorphism of androgen receptor(AR)with ovarian reserve and ovarian response in controlled ovarian stimulation(COS).Methods This genetic association study was conducted among a total of 361 women aged≤40 years with basal FSH≤12 U/L undergoing the GnRH-agonist long protocol for COS in a university affiliated IVF center.GGN repeat in the AR gene was analyzed with Sanger sequencing.The primary endpoint was the number of antral follicle counts(AFCs),and the secondary endpoints were stimulation days,total dose of gonadotropin(Gn)used,total number of retrieved oocytes,ovarian sensitivity index,and follicular output rate.Results The GGN repeat in exon 1 of the AR gene ranged from 13 to 24,and the median repeat length was 22.Based on the genotypes(S for GGN repeats<22,L for GGN repeats≥22),the patients were divided into 3 groups:SS,SL,and LL.Generalized regression analysis indicated that the number of AFCs in group SS was significantly lower than those in group SL(adjusted β=1.8,95%CI:0.2-3.4,P=0.024)and group LL(adjusted β=1.5,95%CI:0.2-2.7,P=0.021).No significant difference was observed in the number of AFCs between group SL and group LL(P>0.05).Generalized regression analysis indicated no significant differences in ovarian stimulation parameters among the 3 groups,either before or after adjusting for confounding factors(P>0.05).Conclusion GGN repeat length on the AR gene is associated with AFC but not with ovarian response in Chinese women,indicating that AR gene polymorphisms may affect ovarian reserve.
文摘The heterogeneity of triple-negative breast cancer(TNBC)has spurred the exploration of precision therapies based on molecular subtypes,with the androgen receptor(AR)-positive subtype emerging as a potential therapeutic target.The treatment of AR-positive TNBC relies primarily on androgen receptor antagonists,such as enobosarm,bicalutamide,and enzalutamide.To enhance efficacy,researchers are investigating combination therapies that integrate anti-androgen agents with chemotherapy,immunotherapy,or PARP inhibitors.Additionally,studies have revealed that the AR signaling pathway regulates the tumor microenvironment,and AR inhibition may potentiate the efficacy of immune checkpoint inhibitors.However,anti-AR therapies face significant limitations and challenges due to multifaceted factors,necessitating further resolution.With continued advancements,AR-targeted therapy holds promise as a critical component of personalized treatment strategies for TNBC.
文摘BACKGROUND Vitamin D deficiency has been associated with prostate cancer,particularly in ethnic minorities.Patients with prostate cancer may still be deficient even in areas of high sun exposure.Although androgen deprivation therapy(ADT)is well documented to affect bone health,its impact on vitamin D levels is still uncertain.This study investigates the subgroups of prostate cancer patients most associated with vitamin D deficiency and ADT’s relation to this.AIM To examine how prevalent vitamin D deficiency is among prostate cancer patients in a sun-rich environment,with focus on differences by race and disease stage.It also assessed whether ADT is associated with changes in vitamin D levels.METHODS Prostate cancer patients treated at Chao Family Comprehensive Cancer Center between 2014-2024 were retrospectively studied with regards to vitamin D levels across racial groups,disease stages,and ADT exposure.Changes in vitamin D levels pre-and post-ADT over 24 months were assessed by statistical methods including paired t-tests.RESULTS Among 120 patients(mean age:74 years,mean body mass index:27.6 kg/m^(2)),African American(33.3%)and Hispanic(31.8%)patients had the greatest prevalence of vitamin D deficiency(<20 ng/mL).With a 28.6%deficit rate,metastatic castration-resistant prostate cancer had the highest prevalence rates of deficiency.There was no significant difference between pre-and post-ADT vitamin D levels(P=0.45).CONCLUSION Vitamin D deficiency is common in prostate cancer patients,especially racial minorities and those with advanced disease,despite residing in an area with high sun exposure.ADT does not significantly impact vitamin D levels in the short term.Routine screening and supplementation should be considered in these high-risk groups.
文摘Prostate cancer is the most common non-cutaneous cancers occurring in American men,and whilemost men with early-stage prostate cancers are cured,up to a third might manifest with biochemical recurrence(BCR)of prostate cancer.BCR is a disease entitywhich is characterized by a rising prostate-specific antigen(PSA)in the setting of a previously treated localized prostate cancerwith either surgery or radiation therapywith curativeintent.
文摘Background:Intermediate-risk prostate cancer(IR-PC)represents a heterogeneous group requiring nuanced treatment approaches,and recent advancements in radiotherapy(RT),androgen deprivation therapy(ADT),and prostatespecific membrane antigen positron emission tomography(PSMA-PET/CT)imaging have prompted growing interest in personalized,risk-adapted management strategies.This study by the Turkish Society for Radiation Oncology aims to examine radiation oncologists’practices in managing IR-PC,focusing on RT and imaging modalities to identify trends for personalized treatments.Methods:A cross-sectional survey was conducted among Turkish radiation oncologists treating at least 50 prostate cancer(PC)cases annually.The 22-item questionnaire covered IR-PC management aspects such as risk stratification,imaging preferences,androgen deprivation therapy(ADT)use and duration,RT techniques,and treatment combinations.Anonymous responses were analyzed using descriptive statistics.Results:Thirty radiation oncologists participated,57%with over 20 years of experience.The median annual number of PC cases treated was 130.For risk stratification,43% followed the National Comprehensive Cancer Network(NCCN)guidelines,while 30%used the D’Amico classification.Imaging preferences revealed 47% favored PSMA-PET/CT.External beam RT was universally preferred,with 60% adopting ultra-hypofractionation.ADT was used by 97%,with 73% recommending it for unfavorable IR-PC cases.Short-term ADT(4–6 months)was the standard,administered concurrently with RT by 57%.Cardiovascular status influenced decisions for 97% of respondents,while 37% also considered patient age,preferences,and sexual health.Conclusions:This national survey demonstrates a shift toward personalized care in intermediate-risk prostate cancer in Turkey,marked by selective PSMA-PET/CT use,tailored ADT,and evolving radiotherapy practices.The findings underscore the importance of multidisciplinary collaboration—particularly between urologists and radiation oncologists—to optimize imaging integration and treatment outcomes.
文摘The mechanism of androgen action is complex. Recently, significant advances have been made into our understanding of how androgens act via the androgen receptor （AR） through the use of genetically modified mouse models. A number of global and tissue-specific AR knockout （ARKO） models have been generated using the Cre-loxP system which allows tissue- and/or cell-specific deletion. These ARKO models have examined a number of sites of androgen action including the cardiovascular system, the immune and hemopoetic system, bone, muscle, adipose tissue, the prostate and the brain. This review focuses on the insights that have been gained into human androgen deficiency through the use of ARKO mouse models at each of these sites of action, and highlights the strengths and limitations of these Cre-loxP mouse models that should be considered to ensure accurate interpretation of the phenotype.
文摘Androgens play a prominent role in the development, maintenance and progression of prostate cancer. The introduction of androgen deprivation therapies into the treatment paradigm for prostate cancer patients has resulted in a wide variety of benefits ranging from a survival advantage for those with clinically localized or locally advanced disease, to improvements in symptom control for patients with advanced disease. Controversies remain, however, surrounding the optimal timing, duration and schedule of these hormonal approaches. Newer hormonal manipulations such as abiraterone acetate have also been investigated and will broaden treatment options for men with prostate cancer, This review highlights the various androgen-directed treatment options available to men with prostate cancer, their specific indications and the evidence supporting each approach, as well as patterns of use of hormonal therapies.
文摘Mutations in the X-linked androgen receptor （AR） gene cause androgen insensitivity syndrome （AIS）, resulting in an impaired embryonic sex differentiation in 46,XY genetic men. Complete androgen insensitivity （CAIS） produces a female external phenotype, whereas cases with partial androgen insensitivity （PALS） have various ambiguities of the genitalia. Mild androgen insensitivity （MAIS） is characterized by undermasculinization and gynecomastia. Here we describe a 2-month-old 46,XY female patient, with all of the characteristics of CAIS. Defects in testosterone （T） and dihydrotestosterone （DHT） synthesis were excluded. Sequencing of the AR gene showed the presence in exon 6 of a T to C transition in the second base of codon 790, nucleotide position 2369, causing a novel missense Leu790Pro mutation in the ligand-binding domain of the AR protein. The identification of a novel AR mutation in a girl with CAIS provides significant information due to the importance of missense mutations in the ligand-binding domain of the AR, which are able to induce functional abnormalities in the androgen binding capability, stabilization of active conformation, or interaction with coactivators.
文摘Aim: To study the effect of androgen and antiandrogen on the level of androgen receptor (AR) mRNA. Methods: The total RNA was extracted from the prostate and analyzed by slot blot analysis. The blots were hybridized with AR cDNA probe and 1A probe (internal control) and autoradiography was performed. The intensity of signal was measured with a densitometer and the ratio of AR RNA and 1A RNA was calculated. Results: Androgenic deprivation produced by castration decreased the weight of the prostate and increased the levels of AR mRNA. Treatment of the castrated rats with testostrone increased the weight of prostate and decreased the levels of AR mRNA. Treatment of normal rats with flutamide decreased the weight of the gland and increased the levels Of AR mRNA. Conclusion: Androgens produce proliferative effect on the prostate and negatively regulate the AR transcription.
基金Acknowledgment We thank Dr Etty N. Benveniste （University of Alabama at Birmingham, Birmingham, AL, USA） for the truncated MMP-2 promoter-driven luciferase constructs and Ms Donna Barnes for excellent secretarial assistance. This study was supported by KU William L.Valk Endowment and Kansas Mason＇s Foundation, and a grant from KUMC Lied Foundation to Dr Ben-Yi Li. This study was also partially supported by grants from the National Natural Science Foundation of China （No. 30370509 and No. 30370645） to Dr Ping-Yi Xu.
文摘Aim： To characterize the matrix metalloproteinases （MMP）-2 promoter and to identify androgen response elements （AREs） involved in androgen-induced MMP-2 expression. Methods： MMP-2 mRNA levels was determined by reverse transcription-polymerase chain reaction （RT-PCR）. MMP-2 promoter-driven luciferase assays were used to determine the fragments responsible for androgen-induced activity. Chromatin-immunoprecipitation assay and electrophoretic mobility shift assays （EMSA） were used to verify the identified AREs in the MMP-2 promoter. Results： Androgen significantly induced MMP-2 expression at the mRNA level, which was blocked by the androgen antagonist bicalutamide. Deletion of a region encompassing base pairs -1591 to -1259 （relative to the start codon） of the MMP-2 promoter led to a significant loss of androgen-induced reporter activity. Additional deletion of the 5＇-region up to -562 bp further reduced the androgen-induced MMP-2 promoter activity. Sequence analysis of these two regions revealed two putative ARE motifs. Introducing mutations in the putative ARE motifs by site-directed mutagenesis approach resulted in a dramatic loss of androgen-induced MMP-2 promoter activity, indicating that the putative ARE motifs are required for androgen-stimulated MMP-2 expression. Most importantly, the androgen receptor （AR） interacted with both motif-containing promoter regions in vivo in a chromatin immunoprecipitation assay after androgen treatment. Furthermore, the AR specifically bound to the wild-type but not mutated ARE motifs-containing probes in an in vitro EMSA assay. Conclusion： Two ARE motifs were identified to be responsible for androgen-induced MMP-2 expression in prostate cancer cells.
文摘Serum testosterone does not correlate with androgen tissue activity, and it is critical to optimize tools to evaluate such activity in males. Ultrasound measurement of bulbocavernosus muscle （BCM） was used to assess the relationship between the number of CAG repeats （CAGn） in the androgen receptor （AR） and the BCM size; the changes in the number of CAGn over age were also evaluated. Transperineal ultrasound measurement of the BCM was also performed. AR CAGn were determined by high performance liquid chromatography, and morning hormone levels were determined using immunoassays. Forty-eight men had CAG repeat analysis. Twenty-five were 〈30 years of age, mean 23.7 years （s.d, = 3.24） and 23 were 〉45 years of age, mean 53years （s.d. = 5.58）. The median CAGn was 21 （13-29）. BCM area was greater when the number of CAGn were 〈18 as compared to the number of CAGn 〉24 （P= 0.04）. There was a linear correlation between the number of CAGn and the BCM area R^2= 16% （P= 0.01）. In the 45 to 65-years-old group, a much stronger negative correlation （R^2 = 29%, P= 0.01） was noticed. In the 19 to 29-years-old group, no such correlation was found （R2 = 4%, P = 0.36）. In older men, the number of CAGn increased with age （R^2 = 32%, P= 0.01）. The number of CAGn in the AR correlates with the area of the BCM. Ultrasound assessment of the BCM is an effective surrogate to evaluate end-organ activity of androgens. The number of CAGn may increase with age.
文摘Androgen doping in power sports is undeniably rampant worldwide. There is strong evidence that androgen administration in men increases skeletal muscle mass, maximal voluntary strength and muscle power. However, we do not have good experimental evidence to support the presumption that androgen administration improves physical function or athletic performance. Androgens do not increase specific force or whole body endurance measures. The anabolic effects of testosterone on the skeletal muscle are mediated through androgen receptor signaling. Testosterone promotes myogenic differentiation of multipotent mesenchymal stem cells and inhibits their differentiation into the adipogenic lineage. Testosterone binding to androgen receptor induces a conformational change in androgen receptor protein, causing it to associate with beta-catenin and TCF-4 and activate downstream Wnt target genes thus promoting myogenic differentiation. The adverse effects of androgens among athletes and recreational bodybuilders are under reported and include acne, deleterious changes in the cardiovascular risk factors, including a marked decrease in plasma high-density lipoproteins （HDL） cholesterol level, suppression of spermatogenesis resulting in infertility, increase in liver enzymes, hepatic neoplasms, mood and behavioral disturbances, and long term suppression of the endogenous hypothalamic-pituitary-gonadal axis. Androgens are often used in combination with other drugs which may have serious adverse events of their own. In spite of effective methods for detecting androgen doping, the policies for screening of athletes are highly variable in different countries and organizations and even existing policies are not uniformly enforced.
基金National Natural Science Foundation of China(82074105)National Key Research and Development Project of China(2021YFC1712904)Science and Technology Program of Tianjin(22ZXGBSY00020,21ZYJDJC00070).
文摘Benign prostatic hyperplasia(BPH)is a common urological condition in aging men.High levels of androgens,including testosterone(T)and dihydrotestosterone(DHT),are closely associated with BPH occurrence and development.Currently,the main clinical drugs used for BPH treatment are 5α-reductase inhibitors andα-receptor blockers,both of which aim to decrease abnormal androgenic signaling while having several unignored side effects.Recently,various natural herbs,such as tonifying yang traditional Chinese medicine(TCM),have been found to have androgenic activities,some of which are also effective for BPH treatment.Here,we review the androgenic activities of phytoandrogens,together with their therapeutic effects in BPH,and summarize the mechanisms involved,providing evidence that such herbs serve as selective androgen receptor modulators.
文摘Objective To investigate the androgen receptor （AR） mRNA expression in pancreas, hypothalamus and ovary of androgen sterilized rats （ASR）.Methods ASR model was established by subcutaneous injection of testosterone propionate to SD female rats at the age of 9 days. Around the age of 106 days （proestrus）, all rats were killed, serum Δ4-andronestedione （Δ 4-A）, total testosterone （TT）, free testosterone （FT）, insulin （Ins） and C-peptide （C-P） were measured by radioimmunoassay （RIA）. Total RNA in pancreas, hypothalamus and ovary were extracted and the amount of AR mRNA was quantitatedly analyzed by RT-PCR with single base mutant template as inner standard. Results Serum concentrations of Δ4-A, TT, FT, Ins and C-P in ASR model rats were significantly higher than those in control group （P〈0.05, P〈0.01）. The expression of AR mRNA in pancreas, hypothalamus and ovary increased significantly （P〈0. 05, P〈0.01） of model rats as compared with control group. Conclusion The elevated serum androgen levels in ASR model could enhance the expression of AR mRNA levels in pancreas, hypothalamus and ovary, which further induce hyperinsulinemia and anovulation.
基金Supported by Scientific research projects under Hebei Provincial Administration of Traditional Chinese Medicine:2011142National Natural Science Foundation of China:8107288381172342
文摘Objective To observe the clinical efficacy of catgut embedment combined with moxibustion and bloodletting in the treatment of androgenic alopecia and to probe into its therapeutic mechanism. Methods Eighty-four patients with androgenic alopecia were divided into catgut embedment group （group A） and western medicine group （group B） on the basis of random number table and according to the order of treatment. For the pateints in group A, Shenguan （肾关） on both sides, Minghuang （明黄） and Zusanli （足三里 ST 36） were selected to receive catgut embedment therapy, once every month, combined with moxibustion on the lower abdomen and local bloodletting treatment. For the patients in group B, finasteride 1mg/d was orally administrated. The treatment period for two groups was 3 months, and the follow-up visit lasted for 3 months. Serum testosterone （T） and estradiol （E2） contents were detected respectively before treatment, after i month and 3 months of treatment and after 3 months of follow-up visit, and the specific values were calculated to make statistical analysis of T, E2, T/E2 and curative effects of the two groups after i month and 3 months of treatment and after 3 months of follow-up visit. Results There was no statistical significance in curative effect between the two groups after i month of treatment （P〉0.05）, and the curative effect in group A were better than that in group B after 3 months of treatment or after 3 months of follow-up visit （both P〈0.05）; E2 level in group A was lower than that in group A after 3 months of treatment （P〈0.05）; T, E2 and T/E2 in group A were all lower than that in group B after 3 month of follow-up visit （all P〈0.05）. Conclusion The curative effect of treating androgenic alopecia with catgut embedment, moxibustion and bloodletting is definite, and its mechanism of action may be related to the reduction of T levels and T/E2 values.
文摘Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
