Factors regulating the influence of melatonin on hippocampal evoked potentials: comparative studies on different strains of mice

Sexual dimorphisms are present throughout the zebra finch song system, from forebrain centers to the tracheosyringeal portion of the hypoglossal nucleus (nXIIts) to the muscles of the syrinx (vocal organ). In females, gonadal steroids administered during development can partially masculinize the telencephalic areas, and in adulthood can increase the size of syrinx muscles. In the present study, two experiments were designed to investigate the role of early androgen and estrogen in the development of nXIIts and the ventralis and dorsalis muscles of the syrinx. In experiment one, males and females were treated with testosterone, estradiol, dihydrotestosterone, the anti-androgen flutamide, or a vehicle control for 21 days after hatching. At day 60, nXIIts volume, motoneuron soma size and number were assessed, as well as syrinx weight and the size of ventralis and dorsalis fibers. In experiment two, animals were administered either the estrogen synthesis inhibitor, fadrozole, or vehicle, and the syrinx measurements were taken at day 60. Male-biased sex differences were detected on all measures in both experiments, and several right-side biases were detected. In females, dihydrotestosterone masculinized soma size in nXIIts and testosterone slightly increased syrinx weight. E2 feminized the syrinx of males. However, flutamide did not prevent masculine development of either structure, and fadrozole did not inhibit feminine syrinx development. These results are consistent with the idea that, as in the forebrain, steroid hormones can stimulate aspects of sexual differentiation, but they may not be direct triggers for the process.     

雄激素对新生大鼠缺氧缺血脑损伤的保护作用及机制研究(英文)

目的：雄激素对缺氧缺血后脑损伤有神经保护作用,但其作用机制尚不完全清楚。该研究探讨雄激素对缺氧缺血性脑损伤(HIBD)的保护作用及其可能的机制。方法：64只7日龄SD大鼠随机分为假手术组、HIBD对照组和雄激素干预组。通过结扎左颈总动脉和吸入8%氧气和92%氮气的混合气体制备新生鼠HIBD模型。假手术组仅做颈正中切口,游离左颈总动脉,不结扎,不行低氧处理。雄激素干预组在模型制成后即刻注射丙酸睾丸酮(25mg/kg)。缺氧缺血(HI)后6h、24h、72h、7d取脑组织制作石蜡切片,用免疫组化法观察Bcl-2和Bax蛋白在各组大鼠皮质和海马表达的动态变化。HI后6h、24h、48h断头取脑制作脑匀浆,测定SOD活性和MDA含量。结果：假手术组大鼠左脑的皮质及海马可见少量Bcl-2蛋白和Bax蛋白免疫阳性细胞表达,与HIBD对照组和雄激素干预组比较差异均有显著性意义(P<0.01)。雄激素干预组HI后6h、24h、72hBcl-2蛋白在皮层和海马的表达水平明显高于HIBD对照组(P<0.05或0.01)。雄激素干预组Bax蛋白的表达水平在HI后24h显著低于HIBD对照组(P<0.05),其他时间点两组Bax蛋白的表达无明显差别。与假手术组比较,HIBD对照组HI后6h大鼠脑组织中SOD活性明显降低,MDA含量明显增加(P<0.05)。HIBD对照组HI后24hSOD活性降至最低值,MDA含量升至最高。雄激素干预增加了SOD活性,雄激素干预组HI后6h、24h、48hSOD活性均明显高于HIBD对照组,差异有显著性意义(P<0.05或0.01)。雄激素干预亦导致了脑组织中MDA含量降低,雄激素干预组HI后6h、24hMDA含量均明显低于HIBD对照组,差异有显著性意义(分别P<0.05、P<0.01)。结论：雄激素发挥脑保护作用可能通过上调Bcl-2蛋白、下调Bax蛋白表达以及通过减少抗氧化剂的消耗和抑制氧自由基的生成,从而减轻缺氧缺血后神经细胞的损伤。     

雄激素等联合治疗老年人骨髓增生异常综合征疗效观察

目的观察雄激素等联合治疗老年人骨髓增生异常综合征(MDS)的疗效和安全性。方法联合应用雄激素、全反式维甲酸、1,25-二羟基维生素D3及小剂量化疗等治疗32例老年MDS,并观察疗效。结果32例患者中完全缓解7例,部分缓解14例,进步4例,无效7例,总有效率为78.1%,副作用为口唇干裂,轻微头痛、头胀等。结论雄激素等联合治疗老年人MDS疗效好,副作用小。     

雄激素受体、孕激素受体在脑膜瘤中的表达及其意义

目的了解雄激素受体(AR)、孕激素受体(PR)在脑膜瘤组织中的表达情况及其与肿瘤良恶性的关系.方法采用免疫组织化学二步法对57例脑膜瘤切片进行AR、PR的检测.结果(1)AR的表达阳性率在全部病例中为50.8%(29/57),良性组为44.4%(20/45),不典型组为60.10%(3/5),恶性组为85.7%(6/7),3组间阳性率的差别有显著性意义(P<0.05).(2)PR表达阳性率在全部病例中为67.9%(38/57),良性组为71.1%(32/45),不典型组为60.10%(3/5),恶性组为42.9%(3/7),3组之间的差别有非常显著性意义(P<0.01).结论PR、AR在良性、不典型性和恶性脑膜瘤中的表达显著不同,检测脑膜瘤中AR、PR的表达可用于判断肿瘤的良恶性,并可能预测其预后.     

Endocrine disrupting compounds and prostate cancer

Prostate cancer is a major health concern and is treated based on its hormone dependence. Agents that alter hormone action can have substantial biological effects on prostate cancer development and progression. As such, there is significant interest in uncovering the potential effects of endocrine disrupting compound (EDC) exposure on prostate cancer. The present review is focused on agents that alter hormone action in the prostate and how they may impact cancer growth or treatment.     

雄激素不敏感综合征30例手术治疗分析

目的 探讨雄激素不敏感综合征（androgen insensitivie syndrome,AIS)患者手术时间、手术方式的选择、发生腹股沟疝的可能以及处理方法。方法 选择1983年11月至2000年7月确诊为雄激素不敏感综合征的患者共30例。对其就诊原因和性腺位于腹股沟的发生率以及误诊的可能性进行总结性分析。结果 30例患者60个性腺中，24个位于腹股沟者为24，占40．0％。单纯以腹股沟包块就诊者5例，占完全型26．7％（4／15），占不完全型6．7％（1／15）。因诊断为腹股沟疝于外院手术者3例（10．0％）。结论 雄激素不敏感综合征因其性腺所处位置的特殊性，易被诊断为腹股沟疝。提醒外科医生接诊女性疝患者时应注意有AIE存在的可能性。因其性腺所具有的功能及恶变可能，性腺应予切除。完全型应在青春期第二性征发育完善后切除。不完全型一经诊断即应切除，同时行外阴整体手术。AIS患者术后应行激素替代治疗（ERT）。     

Development of Gene Therapy Using Prostate-specific Membrane Antigen Promoter/Enhancer with Cre Recombinase/LoxP System for Prostate Cancer Cells under Androgen Ablation Condition

To enhance the efficacy of suicide gene therapy for prostate cancer under androgen deprivation, we designed a promoter system that consists of the prostate-specific membrane antigen (PSMA) promoter/enhancer (PEPM) and Cre-loxP DNA recombination system. We constructed two kinds of plasmids. One plasmid contains a Cre recombinase (Cre) under the control of PEPM and the other expresses CMV-lox-luciferase/herpes simplex virus thymidine kinase (TK). In PSMA-positive LNCaP cells, the promoter activity of the PEPM-Cre plus CMV-lox-luciferase demonstrated 800-fold greater activity compared with that of the PSMA promoter alone. However, no enhancement of the promoter activity was observed in the PSMA-negative cells. Furthermore, in contrast to prostate specific antigen promoter/enhancer (PP), the promoter activity of PEPM did not decrease when the LNCaP cells were cultured in charcoal-stripped fetal bovine serum (CFBS). In an in vitro gene therapy model with LNCaP cells, the cell growth inhibition in the presence of ganciclovir (GCV) was more evident in the cells transfected with the PEPM-Cre plus CMV-lox-TK than in the cells with the PP-TK, and the difference in efficacy between the two plasmids was more remarkable when the cells were maintained in CFBS medium. The therapeutic effect of PEPM-Cre plus CMV-lox-TK was also observed in xenografted LNCaP cells on nude mice when the plasmids were directly injected into tumors and GCV was administered intraperitoneally. These findings indicate that the combination of the PSMA promoter/enhancer and the Cre-loxP system can enhance the PSMA promoter activity even under androgen ablation conditions and can exert its anti-tumor effect both in vitro and in vivo.     

Testosterone protects cerebellar granule cells from oxidative stress-induced cell death through a receptor mediated mechanism

It is known that steroid hormones can affect neuronal susceptibility to different types of insults, including oxidative stress. Using an in vitro/ex vivo model, we have previously shown that cerebellar granule cells prepared from neonatal rats treated with a single dose of testosterone are less vulnerable to oxidative stress-induced cell death, via a mechanism involving an upregulation of the cellular antioxidant defenses. Whether the testosterone protective action on cerebellar granule cells was direct or indirect remained to be clarified. Therefore, in this study we have investigated the effects of in vitro testosterone treatment, to see whether it also protects cerebellar granule cells from oxidative stress-induced damage. Cerebellar granule cells treated with 10(-6) M testosterone for 48 h were found less susceptible to damage induced by 50 microM hydrogen peroxide, as shown by a 30% decrease in the number of cells with apoptotic morphology. The addition of the androgen receptor antagonist flutamide abolished the protective effect of testosterone, suggesting an androgen receptor-mediated mechanism. This hypothesis was further supported by the presence of the androgen receptor in cultured cerebellar granule cells. The activity of the antioxidant enzyme catalase was also measured, and a 2-fold increase was detected in the testosterone treated cells, but not in the cells co-treated with flutamide. The present results demonstrate that cerebellar granule cells treated in vitro with testosterone are protected from oxidative stress via a mechanism mediated by the androgen receptor. Similarly to what we observed after in vivo administration of testosterone, the potentiation of the antioxidant defences seems to play a major role in the protection afforded by testosterone.     

Androgen receptor gene mutation identified by PCR-SSCP and sequencing in 4 patients with complete androgen insensitivity syndrome

To study the genetic defect of the human androgen receptor (hAR) gene in the complete androgen insensitivity syndrome (CAIS), we amplified each of the eight exons by PCR in genomic DNA extracted from the paraffin blocks of the resected gonads. We analyzed using SSCP, and directly sequenced the abnormally shifted bands. Mutations were found in 4 cases of CAIS. Patient 1 carried a point mutation; a G to A transition in exon 7 resulted in a change from arginine to glutamine at codon 831. Patient 2 carried a point mutation; a C to T transition in exon 7 resulted in a change from arginine to stop at codon 831. Patient 3 carried a point mutation and deletion in exon 7. A point mutation was an A to G transition that caused a glutamine to be substituted for the asparagine present at codon 819. A deletion of a G at codon 820 resulted in a frameshift and consequently in the introduction of a premature stop at codon 821. Patient 4 carried a mutation in 5’ splice donor site of intron 7; a G to T transition might have caused an abnormal splicing of the exon 7. All of the mutations were found in exon 7. These mutations of hAR gene might be related to the pathogenesis of CAIS. Received: May 1999 / Accepted: 17 August 1999