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Objective To characterize the expressions of androgen receptor (AR) and estrogen receptor (ER) in penis skin of patients with congenital hypospadias. Methods Dorsal prepuce, ventral prepuce, and urethral plate were harvested from 30 patients with congenital hypospadias. The expressions of AR and ER in epidermal cells and dermal fibroblasts were assessed respectively by automated immunohistochemistry. Image Pro plus 6.0 was used to analyze the optical density (OD) value of AR and ER in different parts of epidermal cells and dermal fibroblasts. Results AR and ER were located mainly in nucleis of the squamous basal cells and prickle cells, and were also found in nucleis of subcutaneous fibroblast cells. The expression of AR was lower in epidermis of urethral plate than that of dorsal prepuce and ventral prepuce (P<0.05), but no significant difference was detected in dermal fibroblasts. The expression of ER was higher in epidermis of dorsal prepuce than that of urethral plate and ventral prepuce (P<0.05). The dermal expression of ER in fibroblast cells was increased successively in dorsal prepuce, ventral prepuce and urethral plate (P<0.05). Conclusion Lower expression of AR in urethral plate may contribute the development of hypospadias. Disorder of ER in dermal fibroblast cells of prepuce may play an important role in hypospadias.
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Objective To explore whether physiological doses of testosterone therapy can modulate cardiomyocyte aging via classical androgen receptor (AR) dependent pathways.Methods Male C57BL/6J mice and testicular feminized (Tfm) mice were divided into five experimental groups:the control group (n=8),the castrated group (n=8),the Tfm group (n=7),the testosterone treated castrated group (n=8),and the testosterone-treated Tfm group (n =8).After isolation of cardiomyocytes from the left ventricle,the activity of superoxide dismutase (SOD) and the amount of malondialdehyde (MDA) were measured using colorimetry,and the expression of the p16INK4a and retinoblastoma (Rb) proteins was detected by Western blotting.Results Compared with the control group,the activity of SOD in the castrated group and the Tfm group declined [(16.55±1.18) U/ml,(17.30±1.32) U/ml vs.(21.57±2.21)U/ml,P＜0.05)],the amount of MDA increased [(7.78±1.27)μmol/L,(6.52±0.82)μmol/L vs.(3.48±0.70)μmol/L],P＜0.01,and the expression of both the p16INK4aand Rb proteins increased [(0.37±0.08),(0.45±0.06) vs.(0.14±0.02),forp16INK4a,P＜0.05; (0.74±0.05),(0.79±0.08) vs.(0.40±0.05),for Rb,P＜0.05].Compared with the castrated group,the activity of SOD in the testosterone treated castrated group increased [(23.00±0.58)U/ml vs.(16.55±1.18) U/ml,P＜0.01],the amount of MDA decreased [(2.63±0.90) μmol/L vs.(7.78±1.27) μmol/L,P＜0.01],and the p16INK4a and Rb proteins were both downregulated (0.13 ± 0.03 vs.0.37± 0.08),for p16INK4a,P＜0.05; (0.45 ±0.05) vs.(0.79±0.08),for Rb P＜0.05.Compared with the Tfm group,the activity of SOD in testosterone-treated Tfm group increased,the amount of MDA decreased,and the p16IN4a and Rb proteins were both downregulated (P＜ 0.05).No significant differences in these markers were detected between the testosterone-treated castrated group and the testosterone-treated Tfm group.Conclusions Physiological doses of testosterone can retard cardiomyocyte aging via androgen receptor independent pathways.
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BACKGROUND:The androgen response to resistance exercise is one of hot topics in sports science research. At present, the androgen responses to resistance exercise show different results. There are different androgen changing trends under different resistance exercise interventions. OBJECTIVE:To have a deep insight into the influence of resistance exercise on the response of human body androgen, clarify research progress in androgen response to resistance exercise, and provide the basic theory for monitoring resistance training. METHODS:Literatures and paper reports about androgen response to resistance exercise are electronical y retrieved from the American Biological Medical Literature Database PubMed from 1986 and 2013. Final y 46 literatures addressing the research progress is analyzed about androgen responses to resistance exercise were included. RESULTS AND CONCLUSION:Studies have shown that, weight lifting (power snatch and power clean), squating, and deadlifting produced higher testosterone levels than the smal muscle groups. Under the same load, eccentric and concentric contractions produced the same hormone response. Adequate training amount and intensity may change the circulating testosterone levels. Short sports intermittent time led to a higher testosterone response than the long intermittent time. The free testosterone levels in youth group were significantly increased compared with the older group before and after exercise. Nutrition intervention affected acute testosterone responses to resistance exercise. Changes in exercise intensity and amount wil alter quiet testosterone levels, once returned to normal training, testosterone levels wil return to baseline values. Resistance exercise can increase androgen receptor content in human skeletal muscles.
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Objective To investigate the relationship of androgen receptor (AR) CAG repeat polymorphism and coronary artery disease (CAD) in elderly men and its potential mechanism.Methods Totally 296 elderly men undergoing coronary angiography were enrolled in this study.Serum total testosterone (TT) and free testosterone (FT) levels were measured.Androgen receptors (ARs) in peripheral lymphocytes were determined by flow cytometry.Genome DNA was extracted from peripheral leucocytes using standard techniques.Gene fragments containing AR CAG repeats were amplified by PCR with specific fluorescent labeled primers.PCR products were separated with agarose gels.CAG repeat number of each sample was obtained by genotyping.Results AR CAG repeats varied from 11 to 28 (P25-P75:18-22; median:20) in elderly male patients.They were divided into the long AR group (CAG repeats≥22,n=82) and the short AR group (CAG repeats＜22,n=214).Compared with the long AR group,serum FT level was much lower in the short AR group [(24.1±23.1) ×10-6mmol/L vs.(31.2±27.8)×10-6mmol/L,P＜0.05].The prevalence of coronary artery disease was higher in the short AR group than in the long AR group [84.1％ (180 cases) vs.69.5％(57 cases),P＜0.05].The FT level was lower in the short AR group combined with CAD than in the control group [(22.4±20.5) ×10-6mmol/L vs.(33.6±32.4)×10 6mmol/L,P＜0.01].There were no significant differences in serum TT and AR levels between the long and short AR groups.No significant correlations were found in the AR CAG repeats polymorphism with FT,TT or AR levels.Age was the main risk factor for FT and AR levels.Logistic regression analysis showed that FT level was negatively correlated with CAD (OR=0.98,95 ％ CI:0.973-0.998,P=0.01),and short AR increased the risk of CAD in elderly male patients (OR=3.44,95％CI:1.887-6.264,P＜0.01).Conclusions Serum FT level is correlated with age and is significantly decreased in elderly male patients with short AR repeats,which may increase the risk of CAD in elderly men.
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Triple-negative (TN) carcinoma is a molecular subtype of breast cancer characterized by the lack of expression of estrogen receptor (ER),progesterone receptor (PR) and HER-2.It is a heterogeneous disease,not only on the molecular level,but also on the pathologic and clinical aspects.TN tumors can be further classified into two subtypes:basal-like,defined as expressing epidermal growth factor receptor (EGFR) and/or cytokeratin (CK) 5/6 by immunohistochemistry,and non-basal-like; the majority of TN tumors are basal-like.TN tumors usually have a more aggressive behaviour and poorer outcome compared with non-TN breast cancers,and lack molecular targets commonly used in targeted therapy,making this group of tumors difficult to treat.Developing novel,effective treatment strategies for these tumors is crucial for improving their prognosis.This review describes a recent study series on prognostic and predictive values of tumor biomarker susing in TN breast cancer patients.TN tumors are associated with significantly higher expression of Ki67 and p53 compared to non-TN tumors.Hormone receptor negativity rather than HER-2 negativity is associated with the increased Ki67 and p53 expression in TN tumors.Furthermore,high expression level of Ki67 ( ＞ 10％ ) but not p53,is significantly associated with nodal metastasis in TN tumors,indicating that Ki67 has better prognostic value than p53.TN tumors with distant metastases are significantly associated with lower expression of androgen receptor (AR) as compared to those with only loco-regional disease ; there is a significant negative correlation between AR and Ki67 expressions among AR expressing TN tumors.Basal-like subtype TN tumors with nodal and distant metastases are associated with significantly higher intratumoral expression of EGFR and CK5/6 as compared to those without metastases.Therefore,increased EGFR and CK5/6 intratumoral expression and decreased AR intratumoral expression,rather than the frequency of their expression,may play a role in the development of metastases and may be predictive of metastatic disease in TN breast cancer patients.Anti-EGFR and anti-AR targeted therapies may provide potential treatment options for TN carcinomas,especially those tumors not responding to chemotherapy.
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Objective: To study the effects of estradiol plus testosterone on the proliferation and apoptosis of breast cancer cell line MCF-7, and to elucidate the possible mechanism. Methods: The growth of MCF-7 cells treated with estradiol (10-10 mol/L) or testosterone (10-5, 10 -7, 10-9 and 10-11 mol/L) alone or in combination for 24, 48 and 72 h was detected by MTT assay. The cell cycle distribution and the apoptosis rate of MCF-7 cells were determined by flow cytometry (FCM). The expression levels of cyclinD1 and androgen receptor (AR) proteins were examined by FCM. Results: The proliferation ability of MCF-7 cells was elevated after treatment with estradiol, and this effect could be inhibited by a higher concentration of testosterone (10-5 mol/L) while improved by a lower concentration of testosterone (10-9 mol/L). After treatment with estradiol plus testosterone (10-5 mol/L) for 48 h, the G1/S phase transition of MCF-7 cells was accelerated, and the apoptosis rate was increased; the expression level of cyclinD1 protein was increased while no change of AR protein expression was observed. Conclusion: Estradiol combined with testosterone of high concentration can inhibit the proliferation of MCF-7 cells and improve the apoptosis. This effect may be associated with the up-regulation of cyclinD1 expression. Copyright© 2011 by the Editorial Board of Tumor.
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Objective The sex hormone and the corresponding receptor may play some roles in the development of the metabolic syndrome (MS) in the elderly men.This study was designed to examine the relationship of level of the sex hormone and androgen receptor with MS in elderly men,thus to investigate the possible pathogenesis of MS.Methods This cross sectional study enrolled 587 elderly men,including 400 healthy controlls aged 62-92 years and 187 MS patients aged 60-87 years in Wan Shou Lu area of Beijing city.Dehydroepiandrosterone sulfate (DHAE-S),total testosterone (TT),sex hormone binding globulin (SHBG),free testosterone (FT),follicle-stimulating hormone (FSH),Estradiol (E2),luteinizing hormone(LH) and androgen receptor (AR) in blood were tested.Statistical analyses included the comparison analysis of variables and independent variables,correlation analysis using multi-factor linear regression,and multiple logistic regression analysis.Results DHAE-S,TT,SHBG,FT and AR fluorescence intensity in healthy control group were higher than those in MS group,however,FSH and E2 levels were lower in healthy group.Age was negatively correlated with diastolic blood pressure (DBP) and FT,but positively correlated with systolic blood pressure (SBP) and E2.AR fluorescence intensity was negatively correlated with SBP and LH.The logistic regression equation showed the negative correlation between DHEA-S,SHBG and the development of MS.Conclusions There are low levels of DHEA-S,TT,SHBG,FT and AR in the elderly patients with MS.On the contrary,FSH and E2 concentration are higher.It can be suggested that low levels of DHEA-S and SHBG may be the potential risk factors of MS in elderly men.
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Objective To study the relationship between a CAG repeat polymorphism of the androgen receptor (AR) gene and postmenopausal osteoporosis (PMO). Methods Genotypes for the AR polymorphisrn were determined by gene scan and DNA sequence methods in a case-control study,including 78 cases of PMO at femoral neck and 73 cases as controls, and 108 cases of PMO at lumbar spine (L2-4) and 60 cases as controls. Bone mineral density for the proximal femur and L2-4 was measured by NORLAND XR-46 dual-energy X-ray absorptiometry. The relationship between the CAG repeat polymorphism and PMO was investigated. Results Eleven different allelic variants,containing 18, 20, 21, 23, 24, 25, 26, 27, 28, 29, and 30 CAG repeats were detected, 16 genotypes were present in the subjects. There were no significant differences in the genotype and allele distributions of (CAG) n polymorphism between PMO group (SS : 25.6 %, SL : 39.7%, LL : 34.6 % ;S:45.5%,L:54.5%) and control group (SS: 23.3%,SL=45.2% ,LL:31.5%;S:45.9%,L:54.1%) at the femoral neck site (all P＞0.05). The risk of PMO at femoral neck in females with the genotypes of SL (0R:0.798,95%CI:0.335～1.797), the LL (0R:0.998,95%CI:0.425～2.341), and the combined SL and LL (OR:0.880, 95% CI: 0.419～1.852) were not significantly increased in comparison with those of females with the SS genotype (all P＞0.05). There were no significant differences in the genotype and allele distributions of (CAG)n polymorphism between PMO group(SS: 18.5%, SL: 49.1%, LL: 32.4%;S:43.1%, L: 56.9%) and control group (SS: 21.7%, SL:45.0% ,LL:33.3% ;S:44.2% ,L:55.8%) at the L2-4 site (P＞0. 05). The risk of PMO at L2-4 in females with the genotypes of SL (OR:1. 276,95%CI:0. 552～2. 950), the LL (OR:1. 137,95%CI:0.468～2.766), and the combined SL and LL (OR: 1. 217,95% CI: 0. 556 ～2. 663 ) were not significantly increased in comparison with those of females with the SS genotype (all P＞0.05). After adjustments for age, postmenopausal period, menopausal age, and body mass index, the logistic regression analyses revealed the (CAG)n polymorphism was not significantly associated with PMO at the femoral neck and L2-4 site (all P＞0.05). Conclusions The CAG repeat polymorphism in the AR gene may not be associated with PMO at the femoral neck and L2-4 site.
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Objective To investigate the changes of sex hormone and androgen receptor levels and evaluate the relationship of the sex hormones and androgen receptor with coronary heart disease (CHD) in elderly men. Methods A cross-sectional study was performed in 539 elderly men, including 400 healthy people aged 62-92 years and 139 CHD patients aged 60-88 years. The plasma concentrations of total testosterone (TT), free testosterone (FT), dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured. The androgen receptor (AR) level was tested by flow cytometry. Results The fluorescence intensity of DHEAS, TT, SHBG, FT and AR were significantly lower in CHD group than in healthy group (P<0.01);however, FSH and E2 in CHD group were higher(P(0.01). Age was negatively correlated with TT(r=-0.28,P<0.01) and FT (r=-0.17,P<0.05), and positively correlated with SHBG(r=0.14,P<0.05) and E2 (r=0.33, P<0.01). AR fluorescence intensity was negatively correlated with systolic blood pressure (r=-0.12,P<0.01). Logistic regression analysis indicated that TT (OR=1.065,9% CI: 1.012～1.121,P<0.05), SHBG(OR=0.994,95% CI:0.990～0.998,P<0.01) and AR (OR=0.971,95%CI:0.956～0.986, P<0.01)were significantly associated with CHD in elderly male patients. Conclusions The levels of DHEAS, TT, SHBG, FT and AR are lower in elderly men with CHD than in elderly healthy men;however, the FSH and E2 concentrations are higher. Low levels of TT, SHBG and AR may be the independent risk factors for CHD in elderly men.
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Objective To study the relationship between polymorphic (CAG)n repeats of androgen receptor(AR) gene and occurrence of prostate cancer (PC). Methods (CAG)n repeats of both malignant cells and adjacent nonmalignant cells from 34 paraffin embedded PCs, and that of peripheral blood cells from 2 PC patients were assessed using dsDNA cycle sequencing. Results The number of (CAG)n repeats in malignant cells was equal to that in adjacent nonmalignant cells from the same paraffin embedded PC; the mean of (CAG)n repeats in the 36 PC patients was 20.06 which was significantly smaller than that of normal men ( P 0.05). Conclusions Shortening of (CAG)n repeats within AR gene may be associated with the occurrence of PC.
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To investigate the expression of androgen receptor (AR) in affected area of androgenetic alopecia (AA) and the relationship between its expression and various syndromes of traditional Chinese medicine (TCM). [Me- thods ]Eighty cases of AA were classified as damp-heat syndrome of spleen and stomach and deficiency syndrome of liver and kidney. Expression level of AR in the alopecia scalp and non-alopecia scalp of the cases was detected with immunohistochemical method and was compared with 32 healthy volunteers.In the cases of AA, AR expression was positive in the granulocyte layer, spinous layer and basal layer of epiderm as well as in the fibroblast, vascular endothelial cells, nerve tissue, arrectores pilorum, sweat gland, sebaceous gland, hair root sheath and hair papilla of dermis;but it was negative in horny layer of epiderm, subcutaneous fat, internal root sheath, hair shaft cells and hair matrocytes. The total AR-positive rate and the AR-positive rate in epiderm, sweat gland, sebaceous gland, hair root sheath and hair papilla were higher in the alopecia scalp of the cases than those in non-alopecia scalp of the cases and in healthy volunteers (P0.05).[Conclusion]AR is related to the pathogenesis of AA and the local abnormal AR content may be one of the pathogenic factors of AA. Pathological feature and AR expression differ with the syndrome patterns: AR expression rate is higher in AA with damp-heat of spleen and stomach than those with deficiency of liver and kidney.
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Objective To diagnose Kennedy's disease (KD) via molecular analysis of the androgen receptor gene with suspected KD.Methods Two patients with suspected KD were reported.We analyzed their clinical features and investigated the number of CAG repeats in the androgen receptor genes. Results Both of the patients were characterized by slow progression of predominant proximal and bulbar muscle weakness.Patient 2 had oligospermatism.Serum creatine kinase and triglyceride levels were found markedly increased.The exact number of CAG was 52 in patient 1 and 48 in patient 2,respectively.These 2 patients were finally diagnosed as Kennedy's disease through the analysis of androgen receptor gene by PCR and direct sequencing.Conclusions The method of molecular analysis for KD had been copied in China.The clinical and molecular biological features of 2 Chinese patients with KD had been discussed.KD is a neurodegenerative disorder by proximal limb muscular atrophy and weakness with lower motor neuron signs,bulbar involvement.Dyscrinism and metabolic abnormalities may also be observed.Gene analysis is the unique and reliable methods to diagnose KD.
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Objective To study the effects of tanshinone on the cultured immortalized human sebocytes and explore the mechanism of action of tanshinone in the treatment of acne. Methods MTT assay was applied to determine the effects of cryptotanshinone and tanshinone Ⅱ? at different concentrations on the proliferation of SZ95 sebocytes in 24 h, 48 h and 72 h after incubation. Lipid contents labeled with Nile red in SZ95 cells were analyzed by flow cytometry technique, and the expression of androgen receptor (AR) mRNA of SZ95 cells were detected by RT-PCR. Results Both cryptotanshinone and tanshinoneⅡ? inhibited the proliferation of SZ95 cells in a dose- and time-dependent mode, with the 50% inhibition concentration (IC50) of 7.473 ?mol/L (in 48 h) and 2.146?mol/L (in 72 h) for cryptotanshinone and 6.021 ?mol/L (in 48 h) and 2.25 ?mol/L (in 72 h) for tanshinone Ⅱ?. Additionally, as compared with the control group, the lipid content of SZ95 cells exposed to tanshinone Ⅱ? at 0.125?mol/L was decreased in 48h (P
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Objective To explore the distributions of C AG polymorphisms of androgen receptor gene in Chinese population and the relatio nship with prostate cancer (CaP). Methods The number of CAG repeats were measured in 105 cases with CaP and 190 matched case-control b y PCR、DHPLC and Sequencing analysis,and its association with the susceptibility to CaP. Results The average number of CAG repeats was 2 2.7 in CaP and 23.3 in control group ( P =0.22).Men with CAG repeats lengt h less than 22 may be in high risk of prostate cancer (odds ratio,2.39;95%CI 1.1 9～4.81, P =0.012),compared with men CAG repeats length of 22 or more. Conclusions A less CAG repeat length (
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Objective To investigate the therapeutic effect of oral viaminate(a vitamine A acid derivative)on acne and its effect on the expression of androgen receptor.Methods Two hundred and eigh-teen patients with acne were allocated to treatment group and control group at random:treatment group was treated by oral viaminate;control group was treated by oral minocycline.The treatment lasted for four weeks.The effect of viaminate on the expression of androgen receptor was studied in COLO-16cells in vitro by using Northern blot or Western blot.Results The therapeutic effect of oral viaminate in treatment group was higher than that in control group(P
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The specific binding capacity of androgen receptor (AR)and estrogen receptor (ER)in the peripheral lymphocytes was estimated by radioligand binding assay in 130 diabetic patients (type Ⅰ 18 cases and type Ⅱ 112 cases). Results were as follows:1)plasma estradiol (E2) of diabetic patients was significantly lower than that of the controls (P