雌雄激素受体与原发性肝细胞癌

原发性肝癌主要是肝细胞癌(HCC)，患者以男性居多．第二军医大学肝胆外科研究所收集1982.1～1991．12月期间手术切除的HCC1000倒．全部经病理检查证实。其中男性899例(89．9％)．女性101例(10．1%)．男女之比为8．9：1。在国外伴有肝硬变的原发性肝癌患者男女之比高达11：1。我们统计了本院建院以来肝癌3017例．男女之比为6．24：1；男性感染HBV、患慢性肝病或饮酒多于女性．便不能完全解释上述差别。从病因及生物学行为方面均提示本病可能与性激素有关。70年代发现肝腺癌的发生与口服避孕药密切相关。在此之后，有许多学者报道用人工合成的雌、雄激素皆能诱发大鼠肝腺瘤及HCC。以上提示原发性肝癌，特别是HCC和性激素及其受体有关。     

尿道下裂患者雄激素受体基因突变的研究

目的研究国人尿道下裂患者雄激素受体基因突变情况。方法采集92例各型尿道下裂患者外周抗凝血,使用酚氯仿变性法提取基因组DNA,通过PCR扩增DNA测序的方法,检测了雄激素受体2～7外显子全部序列。结果4例患者外周血提取的基因组DNA中具有雄激素受体基因外显子突变,第4外显子1例(664ATT→ACT);第7外显子3例(840CGT→CAT、855CGC→CAC、859CTC→CTA)。结论雄激素受体基因点突变可能是尿道下裂的发病原因之一,但是所占比例仅为43%。     

雄激素和雌激素受体与食管癌的关系

目的 通过测定食管癌组织中雄激素受体（AR）和雌激素受体（ER）的含量,探讨食管癌生物学行为与AR和ER的关系。方法 应用放射配体结合分析法定量测定31例食管癌患者癌组织中AR和ER的含量,并与正常食管黏膜组织作对照。结果 与正常食管组织比较,食管癌组织中存在较多的AR和ER,其含量与患者性别、分化程度、浸润程度、有无淋巴结转移有关（P＜0．05）,而与患者年龄、肿瘤的部位无明显关系（P＞0．05）。结论 AR和ER含量与食管癌生物学行为关系密切,可能为食管癌的防治提供新的方法,并作为评价食管癌患者预后的新指标。     

先天性尿道下裂和单纯性阴茎下曲患者阴茎皮肤组织中雄激素受体表达研究

目的观察先天性尿道下裂和单纯性阴茎下曲患者阴茎皮肤组织中雄激素受体(androgen receptor,AR)的表达情况,探讨其在不同程度尿道下裂和阴茎下曲中的表达特征及规律。方法以2005年8月-2007年1月行矫正术的25例先天性尿道下裂和4例单纯性阴茎下曲患者为研究对象,采集阴茎背侧包皮、尿道口腹侧皮肤和尿道板组织。尿道下裂患者年龄1岁11个月～19岁,平均3岁7个月;阴茎下曲患者年龄3岁6个月～16岁,平均7岁1个月。以18例行包皮环切术患者的正常背、腹侧包皮作为对照。免疫组织化学染色观察并检测标本AR的表达水平和分布情况,行统计学分析。结果先天性尿道下裂、单纯性阴茎下曲和正常包皮组织中均有AR表达。正常阴茎背、腹侧包皮AR表达核阳性细胞率分别为62.94%±5.40%、62.87%±5.33%;先天性尿道下裂阴茎背侧包皮、尿道口腹侧皮肤及尿道板组织分别为59.00%±3.75%、58.46%±4.14%、52.30%±3.53%,AR表达均低于正常背、腹侧包皮(P<0.05);且尿道板组织AR表达显著低于自身背、腹侧包皮皮肤(P<0.05),自身背、腹侧包皮皮肤间差异无统计学意义(P>0.05)。与正常背、腹侧包皮比较:远、中段型尿道下裂阴茎背侧包皮AR表达差异无统计学意义(P>0.05),但尿道板组织AR表达显著降低(P<0.05);近段型背侧包皮、尿道口腹侧皮肤及尿道板组织AR表达均降低(P<0.05);下曲<45°者阴茎背侧包皮、尿道口腹侧皮肤AR表达差异无统计学意义(P>0.05),下曲≥45°者比较差异均有统计学意义(P<0.05),两组尿道板组织AR表达均降低(P<0.05)。单纯性尿道下曲患者阴茎背侧包皮、尿道口腹侧皮肤及尿道板组织AR表达核阳性细胞率分别为59.69%±2.73%、55.71%±1.67%、51.92%±1.87%,与正常包皮组织比较,AR表达呈减弱趋势。结论先天性尿道下裂及单纯性阴茎下曲阴茎皮肤组织AR表达低于正常阴茎,尿道板组织AR缺陷突出。     

雌激素受体α基因多态性与东北地区儿童尿道下裂相关性分析

目的:研究雌激素受体α基因(ESR1)rs2077647和rs6932902位点多态性与中国东北地区儿童尿道下裂遗传易感性之间的关联。方法:选取尿道下裂组儿童95例,年龄(3.2±0.6)岁;对照组儿童105例,年龄(3.1±0.7)岁。采用PCR和基因测序检测所有研究对象ESR1基因rs2077647和rs6932902位点的基因型,进行病例对照研究。结果:经PCR和基因测序检测,尿道下裂组和正常对照组rs2077647和rs6932902位点基因型及等位基因分布频率,差异有统计学意义(χ~2=8.552,χ~2=16.251,P0.05);尿道下裂组rs2077647位点单核苷酸多态性的C等位基因比例显著高于正常对照组(51.4%vs 35.8%),差异有统计学意义[OR=1.410(1.130~1.759),P0.05];尿道下裂组rs6932902位点单核苷酸多态性的G等位基因比例明显低于正常对照组(49.5%vs68.1%),差异有统计学意义[OR=2.263(1.503~3.408),P0.01]。尿道下裂组T-A单体型比例显著低于正常对照组(11.93% vs 16.93,P0.05),而C-G单体型显著高于正常对照组(7.06%vs 2.42%,P0.05)。结论:ESR1 rs2077647和rs6932902 2个位点与儿童尿道下裂易感性相关,其构成的单体型也与尿道下裂易感性相关。     

先天性尿道下裂患儿阴茎组织中多种性激素受体的比较研究

为了进一步探讨先天性尿道下裂患儿的内分泌异常,作者应用冰冻切片直接荧光组织化学法对２３例患儿阴茎组织中的雄激素受体、雌激素受体和孕激素受体进行了检测。结果发现：（１）尿道下裂和正常阴茎组织中均有这三种受体的表达,而且它们在尿下裂和正常阴茎组强的含量和分布情况相似,都是ＡＲ含量最高,ＥＲ最低。     

先天性尿道下裂动物模型的建立

我们采用氟丁酰胺能有效干扰孕鼠体内雄激素正常生理作用机制的原理，建立了先天性尿道下裂小鼠模型。     

膀胱癌与性激素、雌激素受体和雄激素受体关系的研究现状

膀胱癌发病率的男性女性比例约为4∶1,有国外学者用动物实验证明雌、雄性小鼠在化学诱导膀胱癌发生中存在差异,随后国内外学者通过大量动物、临床实验和流行病学研究发现了膀胱癌与性激素及其受体存在明确的关系,本文对雌、雄激素及其受体表达量与膀胱癌的发生、发展、转归作一综述.     

雌激素受体α基因SNP12多态性与尿道下裂及隐睾易感性

目的 探讨雌激素受体α基因(ESR1)SNP12(A/G)多态性与尿道下裂及隐睾症发生的相关性.方法 采用PCR及基因测序技术,分别对72例男性尿道下裂患者、31例隐睾患者和40例健康男性儿童外周血基因组DNA ESR1 SNP12(rs6932902)位点的基因多态性进行分析,并与日本、意大利人群比较.结果 尿道下裂组及隐睾组ESR1 SNP12A基因频率均分别高于对照组,差异有统计学意义(出现A等位基因频率,尿道下裂组Vs对照组:50.7%Vs 31.3%,P=0.005,OR=2.2621隐睾组Vs对照组:48.4%Vs31.3%,P=0.038,OR=2.063).结论 ESR1 SNP12 A等位基因可能为发生尿道下裂及隐睾的易感因素,ESR1含SNP12A可能使Erα的信号传导增强,增强了外源性雌激素的雌激素效应,从而使部分个体更容易发生尿道下裂及隐睾.     

hCG调节先天性尿道下裂小鼠阴茎皮肤EGF含量的实验研究

目的:通过建立先天性尿道下裂动物模型,探讨其病因,研究外源性hCG对先天性尿道下裂小鼠阴茎皮肤表皮生长因子(EGF)的影响。方法:建立先天性尿道下裂动物模型。随机选取出生后3周龄正常雄性仔鼠50只腹腔内注射生理盐水1ml作为正常对照组,尿道下裂仔鼠50只,其中10只腹腔内注射生理盐水1ml作为试验对照组,其余40只分为4组,每组10只,腹腔内分别注射hCG(50、100、150、200IU)1次/d,共7d。ELISA法定量检测正常对照组和试验组小鼠阴茎皮肤组织和血清中EGF的浓度。结果:先天性尿道下裂小鼠阴茎皮肤组织EGF的浓度明显低于正常对照组(P<0.05)。hCG注射150、200IU组与尿道下裂生理盐水注射组和hCG注射50、100IU组间小鼠阴茎皮肤组织中EGF的浓度差异有显著性(P<0.05),hCG注射50、100IU组和尿道下裂生理盐水注射组与正常对照组间阴茎皮肤组织中EGF的浓度差异有显著性(P<0.05),小鼠血清中EGF的浓度各组间组内差异无显著性。结论:雄激素受体拮抗剂类药物可造成尿道下裂的发生,小鼠阴茎皮肤组织EGF浓度降低可能与尿道下裂的病因有关。外源性hCG在150～200IU剂量范围内可刺激先天性尿道下裂小鼠阴茎组织EGF浓度的增加。     

Expression of estrogen and androgen receptors in children with hypospadias: preliminary report

This investigation was conducted to evaluate the presence of estrogen and androgen receptors in penile tissues of patients with hypospadias. The biopsy specimens from prepuce, glans, and urethral plate were sampled during the hypospadias surgery in five patients and were analyzed immunohistochemically. Twelve specimens were investigated for the presence of estrogen or androgen receptors (n: 24); the result was negative in 9 (37%) and positive in 15 (63%). Estrogen receptors were present in 10 specimens (42%) (prepuce: 5, glans: 3, and urethral plate: 2). Androgen receptors were present in 5 specimens (21%) (prepuce: 3, glans: 1, and urethral plate: 1). There was expression of both estrogen and androgen receptors in 5 specimens and only estrogen receptors in the remaining 5. Dominant expression of estrogen receptors in penile tissues of children with hypospadias may be the postnatal finding of disrupted estrogen and androgen receptor interaction during the intrauterine development of external genitalia.     

Estrogen receptor immunoreactivity in meningiomas. Comparison with the binding activity of estrogen, progesterone, and androgen receptors

Estrogen receptor (ER) analysis was performed in 70 meningioma samples by means of two assays: an enzyme immunoassay that used monoclonal antibodies against human ER protein (estrophilin), and a sensitive radioligand binding assay that used iodine-125-labeled estradiol as the radioligand. Low levels of ER immunoreactivity were found in tumors from 51% of patients, whereas ER binding activity was demonstrated in 40% of the meningiomas examined. In eight (11%) of the tissue samples, multiple binding sites for estradiol were observed. The immunoreactive binding sites corresponded to those of the classic high-affinity ER. In ligand binding studies, however, measurement of classic ER was considerably influenced by a second low-affinity high-capacity estrogen binding component, even at low ligand concentrations. Binding activity of the progesterone receptor (PR) and androgen receptor (AR) was determined concurrently using 17 alpha-methyl-3H-promegestone (3H-R 5020) and 17 alpha-methyl-3H-trienolone (3H-R 1881), a synthetic gestagen and androgen, respectively. High concentrations of PR were detected in 53 (76%) of the tumors, whereas a moderate number of AR binding sites were demonstrated in 33 (47%) of the tumors. A positive correlation between ER immunoreactivity and AR binding activity is suggestive of estrogen regulation of AR via the ER system. The presence of gonadal steroid receptors in a large proportion of meningiomas and the tendency toward a dependence of receptor concentrations on the histological subtype of the meningioma could have implications for tumor therapy.     

Congenital megalourethra associated with hypospadias

Megalourethra is an extremely rare congenital anomaly. Association with hypospadias has not been previously noted. It is essential that this condition be recognized so that circumcision is not performed. More importantly, other congenital anomalies must be suspected. Onestage surgical repair of the condition is not difficult and generally offers good results.     

Estrogen and progesterone receptors in cerebral meningioma and their clinical value

The contents of receptors of steroid hormones (estrogen and progesterone) in cerebral meningioma was studied up. Comparison between this hormones level and mostly significant clinico-morphological characteristics of meningioma was conducted. High frequency of estrogen and progesterone revealing in the tumor tissue permits to suggest the possibility of their application as a test of her hormonal sensitivity and is important for the disease course prognosis and an adequate methods of treatment choice as well.     

Developmental anomalies and disabilities associated with hypospadias

PURPOSE: The incidence of developmental anomalies and disabilities associated with hypospadias is still a matter of controversy and data on this issue are sparse. We describe our experience with and evaluation of developmental anomalies and disabilities in a population in which posterior hypospadias was the most common anomaly. MATERIALS AND METHODS: We reviewed the records of 356 patients who underwent hypospadias repair from January 1986 through April 2000. Collected data included the Barcat classification of the hypospadias anomaly, anatomical penile variants, associated urogenital and extra-urogenital anomalies, and associated disabilities of physical and mental development. RESULTS: Of the 356 patients 234 (65.7%) had posterior, 88 (24.7%) anterior and 34 (9.6%) mid hypospadias. Anatomical variants, including penoscrotal transposition, bifid scrotum and micropenis, occurred predominantly in patients with posterior hypospadias, while penile torsion was present exclusively in the other 2 groups. Inguinal hernia, which was the most common urogenital anomaly, was distributed evenly among the 3 groups with a prevalence rate of 12.4%. Undescended testis in 26 cases (7.3%) was most often associated with posterior hypospadias. In order of frequency associated extra-urogenital anomalies included congenital heart disease in 19 cases (5.3%), musculoskeletal anomalies in 11 (3.1%), anorectal malformation in 6 (1.7%), cleft palate in 3 and other in 7. In 21 patients (5.9%) associated disorders were related to physical and mental development, including growth retardation in 6, cerebral palsy in 2 and psychological disorders that significantly impaired patient bodily function, behavior and performance in 11. Most extra-urogenital anomalies or disorders were associated with posterior hypospadias. CONCLUSIONS: Posterior hypospadias was the most common anomaly in this study. It was associated with a high rate of extra urogenital anomalies, and physical and psychosocial disabilities. The significance of the latter findings with respect to the development of affected patients needs further clarification.     

A study of quantitative and qualitative abnormality of androgen receptor in patients with hypospadias associated with enlarged prostatic utricle]

The prostatic utricle, a rudimentary structure present in the male prostatic urethra, is currently thought to be of mixed origin, with its cranial portion being derived from müllerian duct and caudal segment from wolffian and müllerian ducts and the urogenital sinus. Enlargement of prostatic utricle has often been demonstrated in patients with hypospadias and its incidence increased according to the severity of hypospadias. It has been suggested that insufficient androgenic stimulation of the urogenital sinus and urethral groove during the critical period of sexual differentiation may cause this entity. Since 5 alpha-dihydrotestosterone (DHT) is a major androgen for the normal development of urogenital sinus, androgen receptor levels in the patients with hypospadias associated with enlarged prostatic utricle may concern this ontogenesis. Fibroblasts derived from penile skin in these patients were assayed for androgen receptor levels using dispersed whole cell binding assay after Eil (1970). Thermostability of androgen receptor in the same fibroblasts was also evaluated by the remaining androgen receptor activity after incubation at 42 degrees C, and expressed as a ratio (percentage) to the androgen receptor activity in the incubation at 22 degrees C. Preputial skin of endocrinologically normal boys in the same range of age (3 to 8 years) was served as controls. There was a significant difference in averages of maximum binding capacities of [3H]DHT to the androgen receptor between those of controls (n = 4) and patients with grade II utricle (n = 4) (89 +/- 5.7 (SE) x 10(2) sites/cell vs. 37 +/- 7.1 x 10(2) sites/cell).(ABSTRACT TRUNCATED AT 250 WORDS)