正常成年男性外阴部皮肤成纤维细胞雄激素受体的研究 Ⅰ.完整细胞受体测定法

本文以[~3H]R1881为配体,建立了正常男性外阴部皮肤成纤维细胞雄激素受体(AR)的完整细胞检测法。实验表明外阴部皮肤成纤维细胞[~3H]R1881的特异结合具有高亲和力、低容量的特点及明显的雄激素结合的特异性,符合AR判定的基本条件。用Scatchard及单点分析法检测了18例我国正常成年男性包皮成纤维细胞[~3H]R1881的特异结合量,其值为6194±982结合位点/细胞((?)±SD)。该法取材比较容易,不需特殊仪器设备,是AR基础与临床研究的简便灵敏的方法。     

男性型脱发患者头皮雄激素受体表达的研究

目的:了解男性型脱发患者头皮雄激素受体(andr ogen r ecept or,AR)表达情况。方法:对来自10例男性AGA患者和3例正常人的头皮,采用免疫组化的方法检测男性型脱发患者头皮不同区域AR的表达。结果:患者不同部位总的AR表达比较,均有明显差异(P<0.05),脱发区最强,且均明显强于正常对照组(P<0.05)。在毛囊隆突部和毛囊漏斗部,脱发交界区及脱发区的AR表达强于枕部非脱发区及正常对照组(P<0.05);在表皮,枕部非脱发区、脱发交界区及脱发区AR表达强度无显著性差异(P>0.05),但均明显强于正常对照组(P<0.05)。在皮脂腺部位,各组的AR表达强度无显著性差异(P>0.05)。结论:男性型脱发患者不同区域头皮AR的表达是有区别的;毛囊隆突部和漏斗部,交界区及脱发区AR表达明显增强,可能是男性型脱发的重要原因之一。     

雄激素不敏感综合征临床诊治分析（附6例报告）

目的：探讨雄激素不敏感综合征（androgen insensitivity syndrome,AIS）患者临床诊断和治疗方法,提高对AIS的诊治效率。方法：回顾性分析我院1985年9月~2012年6月收治6例AIS患者的临床特征,诊断与处理。所有患者均进行了染色体,性激素六项,下腹部B超,术中切除组织病理检测等检查,其中5例患者给予手术切除性腺组织,术后给予小剂量雌激素治疗,1例给予保守治疗。结果：AIS患者多以原发闭经就诊,染色体核型均为46,XY。性激素六项中除了睾酮和LH升高外,其余项未见明显异常。术中切除组织病理检查提示睾丸间质细胞和支持细胞组成的正常睾丸组织,未发现睾丸肿瘤。所有手术患者均未出现女性第二性征发育停滞及骨质疏松等性腺切除后并发症。结论：AIS患者多以“原发闭经就诊”,染色体核型分析联合下腹部B超检查均能有助于AIS快速检出,手术切除性腺具有安全行和可行性。同时加强AIS遗传病史家族胎儿染色体筛查有重要意义。     

完全型雄激素不敏感综合征中雄激素受体基因突变的检测与分析

雄激素通过靶器官上特异的雄激素受体而起作用，因雄激素受体的异常而导致雄激素的作用障碍，称雄激素不敏感综合征。作者分析了４例完全型雄激素不敏感综合征患者雄激素受体基因的突变。从雄激素不敏感综合征患者外周血中提取基因组ＤＮＡ，以特异的引物对雄激素受体基因进行聚合酶链反应（ＰＣＲ）扩增，对扩增产物进行单链构象多态性分析（ＳＳＣＰ），筛选出突变的外显子，对突变的外显子直接进行ＰＣＲ产物测序。通过ＰＣＲ－ＳＳＣＰ检查发现，３例患者在外显子Ｅ及１例在外显子Ｈ上有突变。测序证实前３例患者出现点突变，形成提前终止密码。另１例在外显子和内含子交界处插入ＡＴ两个碱基。提前终止密码形成可能是雄激素不敏感综合征的常见机制，本结果进一步提供了这方面的证据。迄今尚未见在拼接部位５’端同时插入两个碱基导致剪切异常引起人完全型雄激素不敏感综合征的报道。本研究方法简便实用，可用于雄激素不敏感综合征的临床诊断和基础研究。     

雄激素受体研究方法及其进展

雄激素受体研究方法及其进展崔毓桂综述张桂元狄福松审校关键词雄激素，雄激素受体中图法分类号Ｑ５７９．１１雄激素对男性胎儿期性别分化、出生后的生长发育、成年后第二性征的形成和维持、生殖功能的调节，都起着至关重要的作用。睾丸内的Ｌｅｙｄｉｇ细胞合成和分泌的...     

男性靶组织中雄激素受体分析及其数据处理方法的比较研究

应用放射配基结合测定法，以R1881为特异配基；分析正常成年男性雄激素靶组织─—外阴皮肤组织中细胞质和核基质雄激素受体（AR），同时分别用Scatchard、woolf和双倒数作图法三种常用数据处理方法详细分析AR的Bmax（Bm）和Kd。结果表明，作为阳性对照和质量控制的6例雄性大鼠肝脏细胞质AR的Bm为4.77±0．61pmol／g蛋白，Kd为9.662.03×10－10mol／L。11例正常男性的细胞质ARBm为24．03±7．19pmol／g蛋白，Kd为15.13±7.06×10－10mol／L；细胞核内AR的Bm为204．37±119．62pmol／g蛋白，Kd为6．38±4．14×10－10mol／L。Scatchard、Woolf和双倒数法分析的结果均一致。提示AR的Scatchard作图分析是稳定可靠的，并且具有显著的实用价值。     

选择性雄激素受体调节子的开发及其治疗应用

雄激素控制着广泛的生理学功能，雄激素受体作为调节雄激素多种生物学作用的甾体类受体，是一种配基诱导的转录因子，雄激素信号系统的异常导致了从性别确定和性状发育到精神和情感失常的许多紊乱，雄激素替代治疗能改善许多临床症状，包括性腺机能低下与骨质疏松，但由于疗效不高和缺少方便给药的安全制剂而受到限制，最近甾体类受体和选择性受体调节子的基因调控技术，为选择性雄激素受体调节子能否解答现行雄激素治疗中存在的问题，提供了通信班下的机会，配基化的雄激素受体转录引发复合物的组成决定了基因调控的特异性。设计用于引发组织和启动子特异基因转录的合成配基提供了开发更有效的雄激素治疗的希望，建立能预测合成配基活性的测试方法是选择性雄激素受体调节子开发的关键。化合物筛选的高效率和基因指纹技术的进步，如微阵列技术和蛋白组学，将加速有效的选择性受体调节子鉴定。     

Study of bone mineral density in Chinese patients with complete androgen insensitivity syndrome

<正> Objective:To explore the characteristics of bone mineral density(BMD)and treatment inChinese patients with complete androgen insensitivity syndrome(CAIS).Methods:Fourteen cases of CAIS were studied retrospectively through analyzing and compa-ring BMD of pre-and post-gonadectomy with healthy Chinese men and women.BMD at the lum-bar spine and the femur were measured by dual energy X-ray absorptiometry(DXA).Results:There were 10 cases of CAIS having pre-gonadectomy DXA,in which 6 cases hadvery significantly reduced lumbar 2-4 BMD[(0.92±0.08)g/cm~2]comparing with both healthymen and women(P<0.01),5 cases had significantly reduced femur neck BMD[(0.89±0.12)g/cm~2]comparing with healthy men(P<0.05).There were 7 cases having 12 post-gonadectomyDXA,in which all lumbar 2-4 BMD[(0.954-0.06)g/cm~2]were reduced very significantly com-paring with both healthy men and women(P<0.01),femur neck BMD[(0.91±0.08)g/cm~2]were also reduced significantly comparing with healthy men(P<0.01)and women(P<0.05).Conclusion:There were different degrees of osteopenia in patients of CAIS,especially inlumbar vertebra.This suggests that both estrogen and androgen play important roles in the ac-quirement and maintenance of peak bone mass.     

Partial androgen insensitivity syndrome with thermolability in the androgen receptor

We report case of partial androgen insensitivity syndrome in a 12-year-old boy referred to our clinic complaining of bilateral gynecomastia and left undescended testicle. Laparoscopy for undescended testicle and bilateral mastectomy were performed, and the left testicle was absent. When skin fibroblasts of the scrotum obtained during surgery were cultured to analyse the androgen receptors, a slight thermolability was observed. Genomic examination of the androgen receptor gene could not detect any mutations.     

Height and bone mineral density in androgen insensitivity syndrome with mutations in the androgen receptor gene

Introduction and hypothesis Androgen insensitivity syndrome (AIS) constitutes a natural model to study effects of androgens and estrogens on growth and bone density. We evaluated height and bone density in patients with AIS with mutations in the androgen receptor (AR) gene. Methods A retrospective analysis was conducted of eight subjects with complete AIS (CAIS) and four with partial AIS (PAIS) submitted to gonadectomy followed by estrogen replacement, and three with PAIS who did not undergo gonadectomy. Standing height and bone mineral apparent density (BMAD) by DXA were measured and compared with male (z _m) and female (z _f) reference populations. The z-scores were compared with a value of zero using the one-sample t-test. Results Final heights of patients with CAIS and PAIS were intermediate between those predicted for females and males. BMAD of the lumbar spine in CAIS and PAIS after gonadectomy and estrogen replacement (z _f = − 1.56 ± 1.04, P = 0.006, and z _m = − 0.75 ± 0.89, P = 0.04) indicated vertebral bone deficit, whereas BMAD at the femoral neck was normal. No patient reported fractures. Conclusion Subjects with AIS had mean final height intermediate between mean normal male and female, and decreased bone mineral density in the lumbar spine. These data suggest an important role for androgens in normal male growth and bone density not replaced by estrogens.     

A 19 year old with complete androgen insensitivity syndrome and juvenile fibroadenoma of the breast

We report a case of a 19-year-old female with complete androgen insensitivity syndrome (CAIS) who was diagnosed with a juvenile fibdroadenoma of the breast. The patient presented at age 18 with primary amenorrhea. She had been raised as a female and went through thelarche at age 13 and adrenarche at age 14. She had two sisters and three maternal aunts with androgen insensitivity syndrome. Physical exam revealed that the patient had no cervix, and a pelvic sonogram confirmed that the uterus was absent. Genetic analysis revealed a 46 XY karyotype. Bilateral intra-abdominal testes were noted on ultrasound and subsequently removed. She was placed on synthetic estrogen replacement therapy. Roughly 1 year following orchiectomy, the patient noticed an enlarging mass in her right breast. Physical exam revealed a roughly 5 cm mobile mass in the upper portion of the nipple-areolar complex. Ultrasound showed a solid mass consistent with a fibroadenoma. Because of the size of the lesion and the patient's hormonal make-up, a fine needle aspirate was obtained. Cytopathology showed large cohesive sheets of ductal epithelial cells, scattered histiocytes, numerous bare nuclei, fragments of fibrous tissue and metachromatic stroma. Some of the stroma was noted to be cellular. The tumor was subsequently excised. Microscopically, the lesion had epithelial and stromal hyperplasia consistent with a fibroadenoma. Phyllodes-like qualities of large size, increased stromal cellularity, and intracanalicular growth ("leaf-like projections") were noted; however, the pathologist found that the florid epithelial hyperplasia and the patient's young age were more compatible with a juvenile fibroadenoma. We describe what we believe to be the first report of a patient with CAIS and a fibroadenoma of the breast. The hormonal imbalance typically found in these patients, combined with the fact that most individuals with CAIS receive exogenous estrogen therapy, suggests that there may be a relatively high incidence of fibroadenoma in these patients.     

Bilateral testicular tumors in androgen insensitivity syndrome

We report on a case of complete androgen insensitivity syndrome with bilateral testicular tumors and a point mutation in the androgen receptor gene. A bilateral gonadecotmy was performed and both of the resected tumors were histologically diagnosed as pure seminoma. Direct sequencing of amplified exons E-G of the androgen receptor gene from the resected tumor identified a CGA to CAA substitution in exon E, resulting in arginine to glutamine replacement at codon 752. To our knowledge, this is the first reported case of androgen insensitivity syndrome with bilateral testicular tumors.     

雄激素不敏感综合征手术治疗及探查结果分析

目的探讨雄激素不敏感综合征(androgen insensitivity syndrome,AIS)患者的性腺切除途径及其临床病理特点。方法回顾性分析1984年6月至2009年3月北京协和医院诊治的74例AIS患者的性腺切除途径、术后病理结果及性腺位置等特点。结果 74例患者均手术切除双侧性腺。其中完全型雄激素不敏感综合征(CAIS)48例,平均年龄22.0岁,有家族史者3例(6.25%),术中探查发现25例双侧性腺均位于盆腔(52.1%),13例双侧性腺均位于腹股沟内(27.1%);不完全型雄激素不敏感综合征(IAIS)26例,平均年龄16.5岁,有家族史者5例(19.2%),术中探查发现3例双侧性腺均位于盆腔内(11.5%),9例双侧性腺均位于腹股沟内(34.6%),10例双侧性腺均为于大阴唇中(38.5%)。CAIS患者中,开腹切除性腺21例,腹腔镜下性腺切除27例;IAIS患者中,9例开腹切除性腺,7例腹腔镜下性腺切除,10例经会阴切除性腺。术后病理证实睾丸肿瘤的发生率为18.9%,恶性肿瘤占4.1%。结论 IAIS的患者就诊和手术的平均年龄均较CAIS患者年轻,IAIS的患者较CAIS患者有家族史的多。双侧性腺位于盆腔的患者中CAIS多于IAIS,性腺降至腹股沟和大阴唇内的患者中IAIS多于CAIS。AIS患者性腺肿瘤发生率较高,一旦确诊应尽早手术治疗;可参考性腺的位置采用经会阴及腹腔镜微创手术切除性腺。     

Fertility after high‐dose testosterone and intracytoplasmic sperm injection in a patient with androgen insensitivity syndrome with a previously unreported androgen receptor mutation

We report on a case of a man with familial, X‐linked, partial androgen insensitivity, in whom a new point mutation in the androgen receptor (AR) ligand‐binding domain (causing a valine‐to‐alanine substitution at codon 686) was identified. High‐dose prolonged testosterone therapy resulted in marked progression in patient's appearance and great improvement in sperm count and characteristics. In combination with intracytoplasmic microinjection, treatment resulted in fertility. This is believed to be the first report of such a case. This case supports high‐dose testosterone therapeutic trial in this condition. Furthermore, it underscores the possibility of achieving fertility with current endocrine and assisted reproduction modalities, making some of these X‐linked AR mutations paternally transmissible.