ABSTRACT
ObjectiveTo investigate the expression of glial cell line-derived neurotrophic factor (GDNF) and androgen receptor (AR) in testicular peritubular cells (TPCs) of cryptorchidism mouse models and explore the theoretical significance of cryptorchidism-induced spermatogenesis dysfunction. MethodsA total of 30 five-week-old male ICR rats were divided randomly by using random number table method into 6 groups. Cryptorchidism was surgically induced in 3 randomly selected groups and the other 3 groups underwent sham surgery as the control groups. On days 4, 7 and 14 after surgery, we harvested the mice testes of the 3 groups and their corresponding control groups, then measured the testicular volumes, analyzed the testicular histopathology and detected the mRNA and protein expression levels of AR and GDNF in TPCs by immunofluorescence, real-time PCR and Western blot. ResultsIn normal control groups, on days 4, 7 and 14 after surgery, the testicular volumes were (125.58±19.22) mm3,(123.45±20.12) mm3, (140.09±13.62) mm3 , respectively. Clear layers of spermatogenic cells were well arranged and abundant sperm cells were found. Peritubular cells were morphologically homogeneous, with slim-spindle appearance and normal cell thickness. The mRNA expression levels of AR were 1.00±0.05, 1.06±0.07 and 1.19±0.13; GDNF mRNA 1.00±0.04, 1.09±0.05, and 1.10±0.07. The protein expression levels of AR were 1.01±0.01, 0.79±0.02 and 1.01±0.04; GDNF protein (18.68±0.43) pg/mL, (14.39±0.36) pg/mL and (16.88±0.37) pg/mL. In cryptorchidism groups, on days 4, 7 and 14 after surgery, the testicular volumes were (115.64±3.91) mm3, (69.51±14.97) mm3 and (44.86±5.56) mm3, respectively. Spermatogenic cells were disorganized, seminiferous tubules were disrupted, peritubular cells shrank, bent and fractured. The mRNA expression levels of AR were 0.76±0.06, 0.53±0.04, and 0.29±0.02; GDNF mRNA 0.72±0.05, 0.42±0.02 and 0.30±0.03. The protein expression levels of AR were 0.54±0.02, 0.98±0.04 and 0.31±0.01; GDNF protein (8.50±0.34) pg/mL, (17.44±0.32) pg/mL and (6.83±0.34) pg/mL. Statistically significant differences (P < 0.05) were found in 7-day and 14-day testicular volumes between control and cryptorchidism groups but not in the 4-day testicular volume (P > 0.05). Testicular volumes, AR and GDNF mRNA and protein expression in control groups had no statistically significant difference (P > 0.05), while those in cryptorchidism groups showed a trend of gradual decline in the amount and the differences between groups were statistically significant (P < 0.05). ConclusionsIn surgery-induced cryptorchidism mice, after the induction, the expression of AR and GDNF in TPCs showed a gradual decrease over time. AR and GDNF play a major role in mediating the TPCs damage in cryptorchidism. This study provides a theoretical basis for mechanism researches of cryptorchidism-induced spermatogenesis dysfunction.
ABSTRACT
AR (androgen receptor) and CCAT2 are two prostate cancer (PCa)-related genes whereas their relationship is not yet reported. AR is the classical major functional gene in PCa progression. CCAT2, a non-coding gene, was identified based on big-data GWAS (Genome-Wide Association Studies) in the year of 2013. Androgen deprivation therapy (ADT) is usually used to treat PCa in the early stage. After persistent androgen deprivation, PCa would generally lead to castration resistant prostate cancer (CRPC), whereas the mechanism is yet unclear. Here we explore the function of AR and CCAT2 in PCa progression, especially their relation in androgen sensitive and insensitive cell model LNCap and DU145. We found a loop between AR and CCAT2 transcription by over-expression and knock-down strategies. In DU145 cells, G-CCAT2 activated AR mRNA level 2. 6 times, while T-CCAT2 inhibited it to 0. 2 times (P<0. 05). In LNCaP cells, G-CCAT2 could activate AR mRNA levels 1. 5 times, and TCCAT2 had no significant effect (P<0. 05). Under overexpression of AR in DU145 cells, the expression of CCAT2 increased 2. 9 times (P < 0. 05). The abundance of CCAT2 decreased to 0. 48 (P < 0. 05) in LNCaP cells by AR knock-down. Reporter gene analysis showed that CCAT2 could function on the AR promoter. We then performed CCK8 assays and AR protein level detection as supplement for the new gene CCAT2 studies. Finally we primarily studied some target genes that are related to AR and CCAT2 . The results showed that the G-CCAT2 transcript could activate AR expression in LNCap cells while UCCAT2 had no significant effect. In DU145 cells, G-CCAT2 exhibited a more relative stronger activation effect on AR, and U-CCAT2 could inhibit AR transcription. AR activates the transcriptional activity of CCAT2 in both cell lines, suggesting a feedback regulation between them. Our data showed that there would be a feedback loop between CCAT2 and AR, which may indicate a new method for PCa treatment.
ABSTRACT
Objective:To explore the efficacy and mechanism of Guben Qingyuan prescription combined with androgen deprivation therapy (ADT) in the treatment of castration-resistant prostate cancer (CRPC). Method:A CRPC-bearing mouse model was established. When the tumor volume reached about 100 mm<sup>3</sup>, 50 CRPC-bearing BALB/c nude mice were randomly divided into the model group, ADT group, and ADT+low-, medium-, high-dose Guben Qingyuan prescription groups, with 10 mice in each group. After grouping, it was ensured that there was no statistically significant difference in tumor volume between groups. The mice in the model group was treated with the same amount of normal saline (10 mL·kg<sup>-1</sup>) by gavage, twice a day, while those in the other groups were provided with bicalutamide (5 mg·kg<sup>-1</sup>) for intragastric administration, once a day, and then with goserelin (0.36 mg·kg<sup>-1</sup>) for intraperitoneal injection on the 10th day. On the basis of ADT, the ones in the ADT+Guben Qingyuan prescription groups further received Guben Qingyuan prescription at the low (2.5 g·kg<sup>-1</sup>), medium (25 g·kg<sup>-1</sup>), and high doses (50 g·kg<sup>-1</sup>) by gavage, twice a day. After 25 days of continuous administration, the tumor tissue was harvested for recording the tumor growth and calculating the tumor inhibition rate. The mRNA and protein expression levels of androgen receptor (AR), androgen receptor splice variant-7 (AR-V7), and prostate-specific antigen (PSA) were detected by real-time polymerase chain reaction (Real-time PCR) and Western blot assay. Result:The tumor inhibition rates of the ADT+low-, medium-, and high-dose Guben Qingyuan prescription groups were 27.95%, 46.71%, and 44.46%, respectively, and the inhibition rates in the ADT+medium- and high-dose Guben Qingyuan prescription groups were significantly increased as compared with that in the ADT group (<italic>P</italic><0.05). As revealed by comparison with the ADT group, Guben Qingyuan prescription at the medium and high doses significantly down-regulated the mRNA and protein expression levels of AR, AR-V7, and PSA (<italic>P</italic><0.05). Conclusion:Guben Qingyuan prescription combined with ADT is efficient in controlling the tumor growth in CRPC-bearing mice, which is related to the regulation of AR/AR-V7 signaling pathway.
ABSTRACT
Testosterone (T) is a key member of the androgen family, and its biosynthesis is regulated by the hypothalamie-pituitary-gonadal axis, and it is an important hormone that drives sexual differentiation and body development in mammals. The regulatory effects of testosterone on the organism include the androgen receptor (AR) mediated genomic pathway and the non-genomic pathway independent of AR. The genomic approach is that testosterone binds to AR in the cytoplasm through the cell membrane, and then the ligand receptor complex is transferred into the nucleus and combines with androgen response elements (ARE) in the promoter region of the androgen response gene to regulate the downstream gene expression. By binding to receptors on the cell membrane, testosterone rapidly activates related signaling molecules on the membrane and in the cell, and produces effects by initiating transmembrane signal transduction mechanisms, a process known as non-genomic pathway. The heart is the first functional organ formed during embryonic development. Its main function is to provide power for blood flow. Its morphogenesis and function maintenance are closely related to the cell type that constitutes the heart. It is known that the heart is one of the target organs of androgens. In recent years, studies have found that ligand-dependent transcription factor AR is distributed in various cell types of heart tissues, including cardiomyocytes, vascular smooth muscle cells, endothelial cells and cardiac fibroblasts. In addition to affecting gender differentiation and maintaining sexual characteristics, testosterone is also widely involved in the development and function maintenance of many tissues and organs. It also plays an important role in the regulation of cardiac physiological and pathological processes, including participating in heart development, inducing cardiac hypertrophy, regulating cardiac contraction, delaying cardiac aging and affecting vascular calcification. This paper reviews the function of testosterone and its receptor in the main cell types of the heart and their mechanism of action on cardiac physiological and pathological processes in order to provide a reference for the study of the mechanism of action of androgens in the heart.
ABSTRACT
p21-activated kinase 6 (PAK6) is a member of the PAK family of serine/threonine kinases that are known effectors of Rho GTPases Cdc42 and Rac. PAKs regulate a large number of complex cellular mechanisms, including cell motility, morphology, and tumor development. PAK6, initially cloned as an interacting partner of the androgen receptor (AR), is associated with an array of cellular processes implicated in tumor progression. However, the full biological implications of PAK6 activity during cancer remain poorly understood. In this review, we assess our current understanding of the physiological roles of classical PAK6 functionality in mammals, in addition to its emerging role in tumorigenesis.
ABSTRACT
O lincRNA PVT1 (Plasmacytoma Variant Translocation 1) é um RNA longo não codificador de proteínas (ncRNA) descrito como um oncogene sendo superexpresso em vários tipos de cânceres. LincRNA PVT1 está localizado na região genômica 8q24, também conhecida como 'gene desert'. O nível de expressão do lincRNA PVT1 está associado ao aumento do risco de câncer de próstata (PCa) e está correlacionado com os níveis de expressão do receptor de andrógeno (AR). No entanto, o mecanismo do envolvimento do lincRNA PVT1 com o AR no desenvolvimento de câncer de próstata ainda não está bem esclarecido. Aqui, nós testamos a hipótese que a formação do complexo AR-EZH2-PVT1 participa na regulação da expressão gênica em câncer de próstata, nas células LNCaP. A imunoprecipitação de ribonucleoproteínas seguida de PCR quantitativo (RIP-qPCR) revelou que o lincRNA PVT1 está associado fisicamente ao AR (12% do input) e à metiltransferase EZH2, proteína componente do complexo repressor Polycomb 2 (36% do input) sob condições suplementadas com andrógeno (+R1881). O lincRNA PVT1 também está associado fisicamente ao AR (10% de input) e à EZH2 (42% de input) em condições de privação de andrógeno (-R1881). Assim, a associação física entre lincRNA PVT1, AR e EZH2 é independente do hormônio andrógeno. Usando uma abordagem de estudo em larga-escala de perda e ganho de função, nossos resultados mostraram que o silenciamento do lincRNA PVT1 em células LNCaP na presença de andrógeno restaura a expressão parcialmente, totalmente ou causa superexpressão de 160 genes que tiveram a expressão inibida por andrógeno. Entre esses genes, destacamos genes envolvidos na regulação da diferenciação celular, em componentes da junção célula-célula, na inibição da migração e invasão celular e no desencadeamento da via apoptótica. Imunoprecipitação da cromatina seguida de PCR quantitativo (ChIP-qPCR), em cultura de células LNCaP suplementada com andrógeno sob silenciamento do lincRNA PVT1, mostrou aumento significativo na ocupação pela marca de histona ativadora H3K27Ac do promotor do gene NOV, um dos genes que tiveram sua expressão aumentada com o silenciamento de PVT1. O ChIP-qPCR também mostrou, após o silenciamento do lincRNA PVT1, um aumento significativo da marca H3K27me3 na região enhancer do gene NOV, uma característica de enhancers poised (prontos para ativação). Em conclusão, nós fornecemos a primeira evidência experimental para um mecanismo de ação do oncogene lincRNA PVT1 em células de câncer de próstata e demonstramos que sua ação inibidora da expressão afeta genes alvo que facilitam a proliferação e migração de células do câncer de próstata, sugerindo que o lincRNA PVT1 é um novo agente no complexo mecanismo de repressão transcricional envolvendo um RNA silenciador, o receptor de andrógeno (AR) e o potenciador de Zeste homólogo 2 (EZH2) no remodelamento da cromatina em células LNCaP
Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) is an oncogene known to be overexpressed in various types of cancer. PVT1 lincRNA is located in the wellknown cancer-related genomic region 8q24, also known as 'gene desert. PVT1 lincRNA level of expression is associated with increased prostate cancer (PCa) risk and is correlated with androgen receptor (AR) expression levels. However, the mechanism of PVT1 and AR involvement in the development of prostate cancer is still unclear. Here, we tested the hypothesis that formation of the complex AR-EZH2-PVT1 participates in the regulation of gene expression in prostate cancer, in LNCaP cells. Ribonucleoprotein immunoprecipitation followed by quantitative PCR (RIP-qPCR) revealed that PVT1 lincRNA binds both the AR (12 % of PVT1 input) and the methyltransferase EZH2 from the Polycomb repressive complex 2 (36 % of input) under androgen-supplemented conditions (+R1881). PVT1 also binds both AR (10 % of input) and EZH2 (42 % of input) under androgen-deprived conditions (-R1881). Thus, PVT1 binding to AR and EZH2 is independent of the androgen hormone. Using a large-scale loss and gain of function approach, our results show that PVT1 knockdown (KD) in LNCaP in the presence of androgen restores the expression partially, fully or causes overexpression of 160 genes that are inhibited by androgen. Among these genes, we highlight genes involved in regulation of cell differentiation, in components of cell-cell junction, in inhibition of cell migration and invasion and in triggering of the apoptotic pathway. Chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR) with LNCaP cells in androgen-supplemented cultures under PVT1 lincRNA knockdown showed a significant increase in occupancy by the histone activation mark H3K27Ac of the promoter region of the NOV gene, one of the genes that had an increased expression upon PVT1 silencing. ChIPqPCR also showed a significant increase upon PVT1 lincRNA silencing of the H3K27me3 histone mark in the enhancer region of the NOV gene, a distinct feature of poised enhancers. In conclusion, we provide first experimental evidence for a mechanism of action of PVT1 lincRNA oncogene in prostate cancer cells, and show that its inhibitory action affects targetgenes that facilitate proliferation and migration of prostate cancer cells, thus suggesting PVT1 lincRNA as a novel lncRNA player in the complex mechanism of transcriptional repression involving a silencer RNA, the androgen receptor (AR) and the Enhancer of zeste homolog 2 (EZH2) in chromatin remodeling in LNCaP cells
Subject(s)
Plasmacytoma , RNA, Long Noncoding/adverse effects , Enhancer of Zeste Homolog 2 Protein/analysis , Androgens/analysis , Prostatic Neoplasms/diagnosisABSTRACT
Objective • To investigate the effects of ovarian granulosa cell androgen receptor splice variant insertion isoform (AR-ins) on the levels of sex hormones and insulin in patients with polycystic ovary syndrome (PCOS). Methods • Seventy-nine control patients (control group) of normal ovulation and one hundred and fifty-four PCOS patients (PCOS group) who received in vitro fertilization embryo transfer in the Assisted Reproductive Department of the International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine from Jun. 2017 to Jun. 2018 were recruited. The sociodemographic information, serum basic hormones and insulin data were collected according to medical history record, and the hormone levels were measured by chemiluminescence. The ovarian granulosa cells and follicular fluids of all the patients were collected. Nested PCR was used to identify the androgen receptor splice variant (AR SV) in the ovarian granulosa cells from PCOS patients, and then they were divided into two groups, i.e., PCOS Wt group (n=39) and PCOS AR-ins group (n=115). The levels of sex hormones and insulin in follicular fluids of the three groups were detected by chemiluminescence. The free androgen index (FAI) was calculated. The sociodemographic information, the levels of sex hormones and insulin in serum and follicular fluid of the three groups were compared by One-way ANOVA, Welch's ANOVA, Kruskal-Wallis H test and chi-square test. Results • Compared with the control group, the levels of serum sex hormone-binding globulin (SHBG) were significantly lower in the PCOS AR-ins group (P=0.000), and the levels of serum total testosterone (TT) (P=0.000), insulin (P=0.001) and FAI (P=0.000) were significantly higher in the PCOS AR-ins group. Compared with the control group and the PCOS Wt group, the differences of SHBG, TT, insulin levels and FAI in the follicular fluid in the PCOS AR-ins group were statistically significant (all P<0.05). Conclusion • PCOS patients with AR-ins have high androgen and insulin levels in serum, and this effect is more pronounced in the ovarian local microenvironment.
ABSTRACT
Introducción El Cáncer de Mama Triple Negativo (cmtn) es un grupo heterogéneo, de dispar evolución y sin terapia blanco específica. En la actualidad, se postula al Receptor de Andrógenos (ra) como un prometedor biomarcador en cmtn. Objetivos En el presente estudio analizamos un grupo de pacientes con cmtn con el fin de definir la prevalencia del Receptor de Andrógenos en nuestra población y correlacionarla con factores pronósticos y predictivos. Material y método Se realizó un estudio retrospectivo de determinación de Receptor de Andrógenos por inmunohistoquímica sobre los tacos histológicos de pacientes con diagnóstico de cmtn. Se correlacionó su expresión con las características clinicopatológicas y el impacto en la sobrevida. Resultados Se analizaron 179 pacientes con cmtn, diagnosticadas desde el 1º de enero de 2008 al 31 de diciembre de 2014. El 34,02% de los tacos fueron positivos para ra por ihq. El ra se correlacionó inversamente con Ki 67 y citoqueratinas basales. No se encontró relación con la sobrevida global ni con la sobrevida libre de enfermedad. Conclusiones El rol biológico del Receptor de Andrógenos esta aún en discusión. El cmtn ra positivo se relaciona con menor proliferación celular y menor presencia de marcadores basales. El presente trabajo no demostró impacto en la sobrevida global y en la sobrevida libre de enfermedad. Se deberá seguir estudiando al ra por su gran potencial como blanco terapéutico
Introduction Triple Negative Breast Cancer (tnbc) is a heterogeneous group, with aggressive evolution and without a specific therapeutic target. The Androgen Receptor (ar) is being postulated as a promising biomarker in tnbc. Objectives In this study, we analyze a group of patients with tnbc aiming to define the prevalence of the ar in our population, and the correlation of ar expression with prognostic and predictive factors and its impact on prognosis. Materials and method A retrospective study of determination of ar by immunohistochemistry was done in histological samples of the patients with an invasive Triple Negative Breast Cancer diagnosis. We correlated its expression with clinicopathologic features and clinical outcome. Results 179 patients with tnbc diagnosed from January 2008 to December 2014, where analyzed. An 34.02% of the samples were positive for ar. The ar inversely correlated with Ki 67 and basal cytokeratin. There wasn't found a correlation with overall survival or disease free survival. Conclusions The biological role of the Androgen Receptor is still on discussion. The positive ar tnbc is linked with less cellular proliferation and less presence of basal markers. Although its role as a prognostic factor couldn't be revealed by this job, ar receptor must be investigated to determinated their potential role as treatment target.
Subject(s)
Humans , Female , Triple Negative Breast Neoplasms , Prognosis , Breast Neoplasms , Receptors, Androgen , AndrogensABSTRACT
Valproic acid (VPA), an anti-epileptic drug, has been reported to cause male sub/infertility. Together with searching for alternative treatments, the degrees to which testosterone levels and sperm quality are decreased under VPA treatment also need to be clarified. This study aimed to investigate the protective effects of Momordica cochinchinensis (MC) aril extract containing antioxidant capacity on adverse reproductive parameters induced with VPA. Rats were divided into 6 groups (control, VPA, 200 mg kg-1 of MC only, 50, 100, 200 mg kg-1 MC+VPA, respectively, n=8 in each). Animals were pretreated with MC extract for 23 days before co-administration with VPA (500 mg kg-1, i.p.) for 10 consecutive days. All reproductive parameters including histology, and expression of androgen receptor (AR), Ki-67, tyrosine phosphorylated proteins, and steroidogenic proteins in testis were examined. The results showed that MC could prevent all reproductive parameters in VPA-treated rats. Moreover, MC+VPA groups showed significant declining of testicular histopathologies compared to VPA group. It also decreased the malondialdehyde level and changes of the testicular StAR, AR, and tyrosine phosphorylated protein expressions. In conclusion, M. cochinchinensis aril extract can prevent adverse male reproductive parameters and essential testicular proteins damages induced with VPA.
Se ha informado que el ácido valproico (VPA), un fármaco antiepiléptico, causa infertilidad masculina. Junto con la búsqueda de tratamientos alternativos, los grados a los que los niveles de testosterona y la calidad del esperma son disminuidos bajo el tratamiento de VPA también necesitan ser aclarados. El objetivo de este estudio fue investigar los efectos protectores del extracto aril de Momordica cochinchinensis (MC) que contiene capacidad antioxidante sobre parámetros reproductivos adversos inducidos con VPA. Las ratas se dividieron en 6 grupos (control, VPA, 200 mg kg-1 de MC solamente, 50, 100, 200 mg kg-1 de MC + VPA, respectivamente; n = 8 en cada uno). Los animales fueron pretratados con extracto de MC durante 23 días antes de la coadministración con VPA (500 mg kg-1, i.p.) durante 10 días consecutivos. Se examinaron todos los parámetros reproductivos, incluyendo la histología, y la expresión de receptor de andrógenos (AR), Ki-67, proteínas fosforiladas con tirosina y proteínas esteroidogénicas en los testículos. Los resultados mostraron que MC podría prevenir todos los parámetros reproductivos en las ratas tratadas con VPA. Además, los grupos MC + VPA mostraron una disminución significativa de las histopatologías testiculares en comparación con el grupo VPA. También disminuyó el nivel de malondialdehído y los cambios de las expresiones testiculares de las proteínas StAR, AR y tirosina fosforiladas. En conclusión, el extracto de aril de M. cochinchinensis puede prevenir los parámetros reproductivos masculinos adversos y los daños esenciales de proteínas testiculares inducidos con VPA.
Subject(s)
Animals , Male , Rats , Testis/drug effects , Plant Extracts/administration & dosage , Valproic Acid/toxicity , Momordica/chemistry , Antioxidants/administration & dosage , Phosphoproteins , Immunohistochemistry , Receptors, Androgen/drug effects , Blotting, Western , Rats, Wistar , Ki-67 AntigenABSTRACT
Monomelic amyotrophy (MA), also known as Hirayama disease, occurs mainly in young men and manifests as weakness and wasting of the muscles of the distal upper limbs. Here, we sought to identify a genetic basis for MA. Given the predominance of MA in males, we focused on candidate neurological disease genes located on the X chromosome, selecting two X-linked candidate genes, androgen receptor (AR) and ubiquitin-like modifier activating enzyme 1 (UBA1). Screening for genetic variants using patients' genomic DNA revealed three known genetic variants in the coding region of the AR gene: one nonsynonymous single-nucleotide polymorphism (SNP; rs78686797) encoding Leu57Gln, and two variants of polymorphic trinucleotide repeat segments that encode polyglutamine (CAG repeat; rs5902610) and polyglycine (GGC repeat; rs3138869) tracts. Notably, the Leu57Gln polymorphism was found in two patients with MA from 24 MA patients, whereas no variants were found in 142 healthy male controls. However, the numbers of CAG and GGC repeats in the AR gene were within the normal range. These data suggest that the Leu57Gln polymorphism encoded by the X-linked AR gene may contribute to the development of MA.
Subject(s)
Humans , Male , Case-Control Studies , Clinical Coding , DNA , Genes, X-Linked , Mass Screening , Muscles , Peptides , Receptors, Androgen , Reference Values , Spinal Muscular Atrophies of Childhood , Trinucleotide Repeats , Upper Extremity , X ChromosomeABSTRACT
Objective To investigate the distribution characteristics of (CAG)n polymorphism in the exonl of the androgen receptor (AR) gene and its relation to the sensitivity of hypoxic training in men of Han nationality from northern China. Methods Sixty five healthy young men of Han nationality completed HiHiLo training under simulated normobaric hypoxic environment for 4 weeks. They stayed under the condition of 14.3-14.8% O_2 (simulating 2800~3000m) during nighttime and carried out hypoxic training under the condition of 14.8-15.4% O_2 (simulating 2500~2800m) 3 times per week at the intensity of 75% individual VO_2max. VO_2max and body weight of the subjects were measured. GeneScan method was used to identify the repeat alleles (genotypes) of CAG polymorphism. Results (1) Fifteen alleles (CAG)12,(CAG)16-28,(CAG)30 repeat alleles (genotypes) were observed in the subjects, in which (CAG)22 was the most common allele; (2) When 21 and 22 alleles were used as the cut point, the baseline of body weight in those carrying shorter genotypes was significantly lower than that in those carrying longer genotypes; (3) △VO_2max and △rVO_2max in men carrying shorter genotypes were significantly higher than that in men carrying longer genotypes after hypoxic training. Conclusion The result reveals that AR (CAG)n polymorphism is associated with the sensitivity of simulated normobaric hypoxic HiHiLo training in men of Han nationality from northern China, especially in those carrying shorter genotypes of AR CAG.
ABSTRACT
I previously reported the PCR-based Spinal and bulbar muscular atrophy (SBMA) region polymorphisms in the three northeast Asian populations (Chinese, Koreans, Japanese) and Caucasians. Here I update this analysis by including the data of the allele distribution in 378 unrelated individuals from four populations in Asia. In this study I investigated PCR-based CAG repeat polymorphism on the SBMA locus among four Asian populations (Mongolian, Evenki, Orochon, Negrito) and performed the statistical analysis on the eight populations including the previously analyzed data. Both statistical analyses of one-way ANOVA (F=3.284, P=0.002) and Kruskal-Wallis test (chi-square=21.542, DF=7, P=0.003) showed remarkable differences in CAG allele distributions among the populations. Post-hoc test showed that the difference between Negritos and Caucasians was especially significant (Scheffe: P=0.042; Bonferroni: P=0.004). Also a significant differences among Northeast Asians, Caucasians and Negritos (Southeast Asian) were detected by these two tests (ANOVA; F=8.132, P.0.000, Kruskal-Wallis; chi-square=16.614, DF=2, P.0.000). Post-hoc test showed that the differences between Negritos and Caucasias was also especially significant (Scheffe: P=0.001; Bonferroni: P=0.000) among these three groups. These data present that the CAG repeat polymorphism of SBMA gene has a useful information for studies of human population genetics.
Subject(s)
Humans , Alleles , Asia , Asian People , Genetics, Population , Muscular Disorders, Atrophic , Trinucleotide RepeatsABSTRACT
Objective To explore the role of androgen receptor (AR) and estrogen receptor (ER) on male pattern baldness (MPB). Methods The contents of AR and ER in donor and recipient sites of scalps after hair autografting were determinated in 13 cases of MPB. Fluorescent steroid hormone conjugate technique was employed in this study. Results There was no statistical difference in the contents of AR and ER between donor site and grafted scalps in recipient site. Conclusion After the donor tissues are transplanted to the recipient site (the former baldness site), there is no change in contents of AR and ER. The abnormal change of the content of AR and ER in scalp plays an important role in MPB development.