性激素和雄激素受体与老年男性糖尿病的相关性研究

目的 研究老年男性糖尿病患者的性激素和雄激素受体水平的变化,探讨老年男性糖尿病患者性激素和雄激素受体与糖尿病的相关性. 方法横断面调查老年男性492例,其中健康对照组104例,平均年龄(71.4±5.2)岁;非糖尿病对照组259例,平均年龄(71.5±5.0)岁;糖尿病组129例,平均年龄(73.0±6.3)岁.测定总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇(E_2)、黄体生成素(LH)、卵泡刺激素(FSH)水平,采用流式细胞术检测外周血白细胞雄激素受体(AR)水平. 结果糖尿病组TT水平显著低于两对照组,分别为(17.1±6.1)、(15.8±6.0)nmol/L和(13.8±4.7)nmol/L(P<0.01),FT、SHBG、AR阳性率、AR荧光强度健康对照组、非糖尿病对照组和糖尿病组3组间呈下降趋势.但差异无统计学意义.多元回归分析町见TT、E_2,E_2/T,SHBG与血糖水平呈负相关;SHBG与糖尿病病程呈正相关.TT和AR阳性率与糖尿病病程呈负相关.Logistic多元同归分析示年龄、腰臀围比、FSH、SHBG、AR阳性率是糖尿病的危险因素. 结论低水平的TT、SHBG和AR可能是糖尿病的危险因素,在老年男性糖尿病的发生和发展中起到一定作用.     

雄激素及其受体与老年男性冠状动脉粥样硬化性心脏病的相关性研究

目的 观察老年男性冠状动脉粥样硬化性心脏病(冠心病)患者性激素及雄激素受体水平的变化及相关性. 方法 横断面调查老年男性539例,其中健康人(对照组)400例,年龄62～92岁,平均(71.4±5.2)岁;冠心病患者139例,年龄60～88岁,平均(73.6±6.4)岁.测定总睾酮、游离睾酮、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇、黄体生成素(LH)、卵泡刺激素(FSH)水平,同时采用流式细胞术检测外周血雄激素受体(AR)水平. 结果 老年男性冠心病患者DHAES、总睾酮、SHBG、游离睾酮、AR荧光强度均低于对照组(均为P<0.01),而FSH、E2高于对照组(均为P<0.01).年龄与总睾酮、游离睾酮呈负相关(r分别为-0.28、-0.17,P<0.01和P<0.05);与E2、SHBG呈正相关(r分别为0.33、0.14,P<0.01和P<0.05).AR荧光强度与收缩压呈负相关(r=-0.12,P<0.01).Logistic回归分析显示,总睾酮(OR=1.065,95%CI:1.012～1.121,P<0.05)、SHBG(OR=0.994,95%CI:0.990～0.998,P<0.01)和AR(OR=0.971,95%CI:0.956～0.986,P<0.01)与老年男性冠心病相关. 结论 老年男性冠心病患者存在低水平的DHEAS、总睾酮、SHBG、游离睾酮、AR,同时存在高水平的FSH、E2;低水平总睾酮、SHBG和AR可能是老年男性冠心病独立的危险因素.     

雄激素及其受体和雌激素变化在老年男性高血压患者中的初步研究

目的探讨老年男性高血压患者的雄激素及其受体以及雌激素水平变化。方法选择172例老年男性高血压患者(高血压组)和104例同龄健康男性(健康组),检测所有入选者血清7种性激素,黄体生成素(LH)、卵泡刺激素(FSH)、总睾酮(TT)和雌二醇(E2)采用化学发光法检测;游离睾酮(FT),硫酸脱氢表雄酮(DHEA-s),性激素结合球蛋白(SHBG)采用酶联免疫吸附法检测。使用流式细胞技术测定外周淋巴细胞的雄激素受体(AR)含量(AR平均荧光强度)。结果(1)与健康组比较,高血压组体重指数(BMI),腰围,腰臀比,空腹血糖和E2/TT明显增高,TT明显下降(P<0.01)(。2)控制BMI因素影响后,与收缩压相关的性激素有TT(P=0.047)和E2/TT(P=0.001);与舒张压相关的因素有E2,E2/TT和AR荧光强度(P<0.05)。结论男性高血压患者TT明显下降、E2/TT明显升高。E2/TT与收缩压和舒张压呈正相关,E2和AR荧光强度与舒张压呈正相关。     

老年男性代谢综合征患者性激素和性激素受体的变化

目的 探讨老年男性代谢综合征患者性激素和性激素受体与老年男性代谢综合征各组分的相互关系. 方法老年男性587例,其中代谢综合征患者187例(代谢综合征组),健康人400例(健康组).测定总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮硫酸酯(DHEAS)、性激素结合球蛋白(SHBG)、雌二醇(E2)、黄体生成素(LH)、卵泡刺 激素(FSH)水平,同时采用流式细胞术检测外周血雄激素受体(AR)水平.结果 代谢综合征组患者DHAES、TT、SHBG、FT、AR荧光强度均低于健康组,而FSH、E2高于健康组.年龄与舒张压、FT呈负相关,与收缩压、E2 呈正相关.AR荧光强度与收缩压、LH呈负相关.DHEAS、SHBG进入logistic回归方程,与代谢综合征的发病呈负相关趋势.结论 老年男性代谢综合征患者存在低水平的DHEAS、TT、SHBG、FT、AR,同时存在高水平的FSH、E2;低水平的DHEAS、SHBG可能是老年男性代谢综合征潜在的危险因素.     

健康老年男性雄激素受体基因CAG重复序列多态性研究

目的研究健康老年男性雄激素受体(AR)基因CAG重复序列多态性。方法使用DNA测序方法对102例健康老年男性AR基因外显子1 NH_2-端转录调节区内CAG重复序列长度进行测定。结果男性AR基因CAG重复数最短为8,最长为35。CAG重复数平均值为22．83±3．97。CAG重复数分布频率最多的为21(17．6%),22 (14．7%),23(15．7%)和24(6．9%),共占54．9%。结论健康老年男性AR基因CAG重复序列呈现多态性,多数集中在21-24。为进一步研究AR基因变异与疾病的关系提供依据。     

雄激素受体及雄激素在老年男性高血压患者中的变化及意义

目的探讨男性高血压患者性激素水平的变化,并进一步研究性激素与高血压患者雄激素受体、肥胖的相关性。方法收集高血压患者112例,正常健康者120例,记录临床资料,包括身高、体重、年龄。采用酶联免疫吸附法及化学发光法检测血浆总睾酮(TSTO),游离睾酮(FT),脱氢表雄酮硫酸酯(DHEAS),性激素结合球蛋白(SHBG),雌二醇(E2),黄体生成素LH),卵泡刺激素(FSH)水平。用流式细胞术测定外周血白细胞雄激素受体(AR),以上各项指标在两组之间进行比较。结果高血压患者总睾酮(TSTO)浓度明显低于正常对照组,差异有显著性(P<0．05)。高血压组体重指数、腰围／臀围、E2／T与正常对照组相比均存在显著性差异(P<0．05)。高血压患者血浆总睾酮与雄激素受体含量、体重指数呈显著相关,分别与雄激素受体含量正相关(r=0．08,P<0．01);与体重指数负相关(r=-0．58,P<0．01)。结论血浆雄激素水平可作为评估高血压发病危险因素的一项新指标。     

雄激素和雄激素受体与老年男性外周动脉硬化闭塞病的相关研究

目的 探讨老年男性外周动脉硬化闭塞病患者的雄激素和雄激素受体水平变化.方法 收集老年男性外周动脉硬化闭塞病患者44例（外周动脉硬化闭塞病组）和男性健康者104例（健康组）,共检测血清中的7种性激素：黄体生成素、卵泡刺激素、总睾酮和雌二醇,采用化学发光法检测;游离睾酮,硫酸脱氢表雄酮和性激素结合球蛋白采用酶联免疫法检测.使用流式细胞技术测定外周淋巴细胞内雄激素受体含量.结果 与健康组比较,外周动脉硬化闭塞病组患者腰围（90.75土8.38）cm νs（86.61±8.91）cm、腰臀比（0.91±0.05 νs0.88±0.06）,收缩压[（140.91±20.55）mm Hg νs（130.03±16.69）mm Hg,1 mm Hg=0.133 kPa]、舒张压（83.07士14.15）mm Hg νs（77.21士9.34）mm Hg和雌二醇/总睾酮比值（7.32±3.32 νs 5.76±2.69）明显增高,而雄激素受体荧光强度（2.92±0.97 νs3.36±1.05）明显下降.结论 老年男性外周动脉硬化闭塞病患者雌二醇/总睾酮比值明显增高,雄激素受体含量明显降低.雄激素受体水平下降可能加速动脉粥样硬化发展.[编者按]     

血清性激素水平与老年女性代谢综合征的关系

目的探讨老年女性血清性激素水平与代谢综合征(MS)的关系。方法选择2013年1月至2014年1月在该院体检的168例绝经后的老年女性,根据检查结果分为健康组(78例)和MS组(90例),测定所有受试者血清中雌二醇(E2)、黄体生成素(LH)、卵泡雌激素(FSH)、性激素结合球蛋白(SHBG)、总睾酮(TT)、游离睾酮(FT)、脱氢表雄酮(DHEA)、血脂、血糖,测量身高、体重和血压。结果健康组三酰甘油(TG)、空腹血糖(FBG)、体重指数(BMI)水平和血压远远低于MS组,高密度脂蛋白胆固醇(HDL-C)远远高于MS组(P>0.05);健康组E2、LH、FSH、SHBG和E2/TT显著高于MS组,而TT显著低于MS组(P<0.05);E2、SHBG与MS及组分间呈负相关(P<0.05),TT与MS及组分呈正相关(P<0.05),且逐步回归分析表明雌激素为MS发病的主要危险因素(P<0.05)。结论女性绝经后性激素急剧降低,增加MS的危险,适当补充雌激素,调节SHBG水平,对于降低MS发病率具有重要意义。     

雄激素受体基因多态性与男性冠心病关系的研究

目的:雄激素受体(AR)基因外显子1区基因片断CAG多态性与男性冠心病(CAD)及其危险因素的关系。方法:125例冠脉造影证实的男性冠心病人均接受检查,CAD严重程度采用冠脉狭窄≥50%的支数(0～3),分别计算心肌梗塞栓塞(TIMI)危险积分,外周血AR转录激活区CAG重复序列的长度采用PCR法测定。结果:CAG重复长度为13～30次,CAG重复≥24次者为长AR基因组,<24次者为短AR基因组。与长AR基因组比较:短AR基因组患者具有较低的平均体重指数(BMI)(t=-3.024,P=0.005)和较低水平的高密度脂蛋白(HDL)(t=-2.610,P=0.010);短AR基因组出现明显冠脉狭窄的可能性较大(x2=4.82,P=0.028),TIMI危险积分较高(M-W检验,z=-2.644,P=0.008)。Spearman相关分析表明,AR基因CAG长度和TIMI危险积分显著负相关(r=-0.230,P=0.010),这种相关性独立于年龄、BMI、LDL、UA和HDL之外(偏相关系数r=-0.250,P=0.006)。结论:具有短AR基因者与更加严重的冠心病相关,提示CAG多态性与男性CAD病情发展相关,AR表达增多,雄激素敏感性增高可能是男性CAD发病率较高的原因之一。     

中老年人群高甘油三酯血症-腰围表型与心血管危险因素聚集关系探讨

目的:探讨40~79岁中老年人群高甘油三酯(TG)血症-腰围(HTWC)表型与心血管危险因素聚集的关系。方法 :利用2013年成都市4个社区横断面流行病学调查的1 004例40~79岁中老年人群数据,将HTWC定义为TG≥2.0 mmol/L,男性腰围≥90 cm,女性腰围≥85 cm。分为(1)TG和腰围正常组(492例)即血TG2.0 mmol/L,男性腰围90 cm,女性腰围85 cm;(2)单纯腹型肥胖组(301例)即血TG2.0 mmol/L,男性腰围≥90 cm,女性腰围≥85 cm;(3)单纯高TG组(79例)即血TG≥2.0 mmol/L,男性腰围90 cm,女性腰围85 cm;(4)HTWC组(132例)即血TG≥2.0 mmol/L,男性腰围≥90 cm,女性腰围≥85 cm,共4组。分析该人群HTWC检出率及其与心血管危险因素聚集的相关性。结果:40~79岁中老年人群HTWC表型的检出率为13.15%(男性12.69%,女性13.37%),40~79岁人群中HTWC组心血管危险因素聚集检出率为41.67%,而TG和腰围正常组心血管危险因素聚集检出率为13.21%。多因素Logistic逐步回归分析显示,经校正年龄、性别、体重指数、吸烟史、糖尿病家族史及高血压家族史后,HTWC组发生心血管危险因素聚集的检出率仍为TG和腰围正常组的4.50倍(比值比:4.50,95%可信区间:2.84~7.12,P0.05)。结论:中老年人群HTWC与心血管危险因素聚集密切相关,可作为筛查心血管危险因素聚集的指标。     

Effect of androgen on androgen receptors in cultured human epididymis

Optimal assay conditions were developed to determine androgen receptor concentrations in samples of human epididymis. Pretreatment of cytosol with mersalyl, as well as the inclusion of molybdate in the homogenization buffers, resulted in a substantial increase in the number of soluble sites detected. A high yield of nuclear and microsomal binding sites was obtained by prolonged incubation (12 h) in 0.6 mol NaCl/l. Organ culture for 6 days resulted in a major loss of androgen-binding sites. In the absence of androgen in the culture media, only 20% of the original sites were found in cultured tissue. Inclusion of dihydrotestosterone (0.1 mumol/l) in the media resulted in samples containing twice as many sites as controls. It is concluded that androgens influence the number of androgen-binding sites in cultured human epididymis in a manner analogous to that described for rat epididymis in vivo.     

雄激素对胸腺内雄激素和雌激素受体的影响

胸腺也是性激素发挥免疫调节作用的靶器官 ,雄激素可以通过胸腺上的多种激素受体来发挥作用。已报道胸腺细胞胞浆中存在雄激素受体 (ＡＲ)和雌激素受体 (ＥＲ) 〔1〕,且雄激素对免疫系统有抑制作用〔2〕,但雄激素对胸腺内性激素受体的影响还不清楚。因此 ,本实验旨在了解雄激素对胸腺内ＡＲ、ＥＲ的调节作用。一、材料和方法1.实验动物及分组 :4 0只 4周龄的ＳＤ大鼠分为正常对照组 (10只 ) ,低剂量、中剂量和高剂量组各 10只 ,按隔日腹腔分别注射 0 .1、0 .5、2 .5ｍｇ丙酸睾酮 (丙睾 )注射持续 2周时间 ,末次注射后 4 8ｈ采血并分离血清用…     

Immunoreactive androgen receptor expression in subjects with androgen resistance.

Individuals with androgen resistance encompass a spectrum of phenotypic abnormalities ranging from complete testicular feminization to undervirilized men. Such subjects have been classified according to the hormone-binding characteristics in genital skin fibroblasts and on the basis of the mutation in the androgen receptor (AR) gene. Antibodies to the amino-terminal region of the human AR were used to develop an immunoblot assay for the comparison of androgen binding with the amount of AR expressed in genital skin fibroblasts. In controls and 4 androgen-resistant subjects with DNA-binding domain mutations, levels of immunoreactive AR correlated closely with androgen-binding capacity. In 15 androgen-resistant subjects with qualitatively abnormal AR, immunoreactive AR levels tended to be higher than predicted from the ligand-binding capacity. Discordance between immunoreactivity and androgen binding also occurred in fibroblasts from 3 other subjects. One carries a stop codon in the AR gene and produces a truncated AR that is immunoreactive but does not bind androgen. Two carry single point mutations in the hormone-binding domain and produce immunoreactive AR that is normal in size but does not bind androgen.     

Mild androgen phenotypes

Mild androgen phenotypes are found in 30-40% of patients referred to an endocrine clinic because of suspected hyperandrogenic syndrome. These disorders are characterized by clinical or biological signs of hyperandrogenism in women with normal ovulatory menstrual cycles. Three main mild androgen disorders may be distinguished: ovulatory polycystic ovarian syndrome (PCOS), idiopathic hyperandrogenism, and idiopathic hirsutism. Ovulatory PCOS includes ovulatory hyperandrogenic patients presenting with polycystic ovaries. Using ESHRE/ASRM criteria for diagnosis of PCOS, this disorder is now part of PCOS spectrum. While in vivo and in vitro studies have confirmed the similarities between the two forms of PCOS, ovulatory PCOS presents clinicians with some unique problems. In fact, fertility is not a problem, but insulin resistance is present, and although milder than in classic PCOS it may be associated with an increased cardiovascular and metabolic risk. Because of this, an ovarian sonography should be performed in all ovulatory hyperandrogenic patients, and when polycystic ovaries are found cardiovascular and metabolic risk should be carefully evaluated. Ovulatory PCOS patients with altered glucose tolerance and/or with dyslipidaemia may need treatment with insulin-sensitizing agents. Idiopathic hyperandrogenism regroups ovulatory patients with increased androgen levels and normal ovaries, while idiopathic hirsutism includes ovulatory patients presenting with hirsutism but normal circulating androgens and normal ovaries. The differentiation between these two disorders may be difficult because commercial assays of androgen levels are generally unreliable. While idiopathic hyperandrogenism may be associated with insulin resistance, neither disorder is associated with an increased cardiovascular risk. The main clinical problem is hirsutism, and this may be approached by aesthetic or pharmacological therapies.     

Structural basis of androgen receptor binding to selective androgen response elements

Steroid receptors bind as dimers to a degenerate set of response elements containing inverted repeats of a hexameric half-site separated by 3 bp of spacer (IR3). Naturally occurring selective androgen response elements have recently been identified that resemble direct repeats of the hexameric half-site (ADR3). The 3D crystal structure of the androgen receptor (AR) DNA-binding domain bound to a selective ADR3 reveals an unexpected head-to-head arrangement of the two protomers rather than the expected head-to-tail arrangement seen in nuclear receptors bound to response elements of similar geometry. Compared with the glucocorticoid receptor, the DNA-binding domain dimer interface of the AR has additional interactions that stabilize the AR dimer and increase the affinity for nonconsensus response elements. This increased interfacial stability compared with the other steroid receptors may account for the selective binding of AR to ADR3 response elements.     

雄激素受体基因新突变致雄激素不敏感综合征

目的 分析2例雄激素不敏感综合征患者及其家系的临床及分子遗传学.方法 收集2例雄激素小敏感综合征患者的临床资料,从患者及其家系成员的外周血单个核细胞抽提基因组DNA,应用PCR扩增雄激素受体基因并直接测序,明确患者及其父母基因有无突变.结果 患者1表现为女性外生殖器、单侧乳房发育、原发性闭经、阴毛腋毛缺如.患者2表现为男性化不全,体毛稀少、双侧乳房发育、尿道下裂.基因检测证实患者1雄激素受体基因第2号外显子第579位密码子点突变(S579N),并证实为一新突变.患者2第5号外显子第747位密码子点突变(V747M).结论 该2例雄激素受体不敏感综合征系分别由雄激素受体基因S579N及V747M所致,其中S579N突变尚未见文献报道.     

Overexpression of androgen receptors in target musculature confers androgen sensitivity to motoneuron dendrites

The dendritic arbors of spinal motoneurons are dynamically regulated by a variety of factors, and several lines of evidence indicate that trophic interactions with the target musculature are of central importance. In highly androgen-sensitive motoneuron populations, androgens are thought to regulate motoneuron dendrites through their action at the receptor-enriched target musculature. Using rats transgenically modified to overexpress androgen receptor (AR) in skeletal muscle, we directly tested the hypothesis that the enhanced expression of AR in the target musculature can underlie the androgenic regulation of motoneuron dendritic morphology. The morphology of motoneurons innervating the quadriceps muscle was examined in wild-type (WT) rats as well as in rats that had been transgenically modified to overexpress ARs in their skeletal musculature. Motoneurons innervating the vastus lateralis muscle of the quadriceps in gonadally intact male rats, and castrated males with or without androgen replacement, were labeled with cholera toxin-conjugated horseradish peroxidase, and dendritic arbors were reconstructed in three dimensions. In WT rats, quadriceps motoneuron dendrites were insensitive to hormonal manipulation. In contrast, quadriceps motoneuron dendrites in gonadally intact transgenic males were larger than those of WT males. Furthermore, overexpression of ARs in the quadriceps muscle resulted in androgen sensitivity in dendrites, with substantial reductions in dendritic length occurring after castration; this reduction was prevented with testosterone replacement. Thus, it appears that the androgen sensitivity of motoneuron dendrites is conferred indirectly via the enrichment of ARs in the musculature.