17β-雌二醇对垂体腺瘤细胞增殖和电压依赖性钾电流的影响

目的　研究 17β 雌二醇 (E2 )对垂体腺瘤GH3细胞增殖和电压依赖性K+ 电流 (IK(V) )的影响 ,探讨IK(V) 与细胞增殖的关系。方法　不同浓度E2作用GH3细胞 ,应用MTT比色法测定细胞增殖 ,流式细胞仪检测细胞周期分布 ,运用全细胞膜片钳技术记录和分析E2对GH3细胞中IK(V) 的作用。结果　E2作用GH3细胞 3d后 ,0 1nmol/L、1nmol/L和 10nmol/LE2组均明显诱导细胞增殖(P <0 0 1) ,并使细胞增殖周期中G0 /G1 期细胞比例下降 ,进入S期细胞增加。E2作用GH3细胞 2 4h后 ,E2以浓度效应关系增加IK(V) 。结论　电压依赖性K+ 通道可能参与E2对GH3细胞的促增殖作用。提示可应用K+ 通道阻断性药物治疗垂体腺瘤。     

白黎芦醇对GH3细胞增殖和PRL合成的影响

目的 探讨白黎芦醇对垂体腺瘤GH3细胞增殖和泌乳素合成的影响，及其对雌激素的拮抗作用。方法 在无血清无酚红的培养条件下，白黎芦醇单独或与雌二醇联合作用于GH3细胞，用MTT法测定细胞增殖，用免疫荧光法、RT-PCR和Western印迹法测定泌乳素的表达情况。结果 白黎芦醇对GH3细胞增殖具有刺激和抑制双相作用，呈时间一剂量依赖性。并且白黎芦醇使GH3细胞中PRL阳性细胞比例下降。同时，白黎芦醇抑制泌乳素的合成。白黎芦醇对雌二醇诱发的细胞增殖和泌乳素合成均有拮抗作用．但对泌乳素合成的拮抗作用较强，而雌二醇刺激细胞增殖作用较其诱发泌乳素合成作用强。结论 白黎芦醇对GH3细胞增殖和泌乳素合成均有抑制作用，从两方面发挥着抗肿瘤作用。     

白黎芦醇对GH3细胞生长和泌乳素合成分泌的抑制作用及其与雌激素受体的关系

目的探讨白黎芦醇（RE）对垂体腺瘤GH3细胞增殖和泌乳素（PRL）合成分泌的影响，及其与雌激素受体（ERs）的关系。方法RE作用于GH3细胞．用免疫荧光法和Western印迹法测定ERs的表达情况．分别用ELISA法和Western印迹法测定培养基内和细胞内PRL水平，用MTT法测定细胞增殖，同时观察了雌二醇（E2）和特异性雌激素受体激动剂对RE的拮抗作用。结果RE改变ERs表达水平，减少PRL合成分泌，抑制GH3细胞增殖，E2和特异性雌激素受体激动剂对RE有拮抗作用。结论RE通过ERs抑制PRL合成、分泌及细胞增殖，从而发挥抗肿瘤作用，两种效应的信号转导途径不尽相同。     

曲格列酮减少CyclinD1的表达抑制体外培养GH3细胞增殖的实验研究

目的 探讨过氧化物酶体增殖激活受体-γ(PPAR-γ)高亲和力配体-噻唑烷二酮类药物曲格列酮对大鼠垂体腺瘤GH3细胞系增殖的影响.并初步探讨其作用机制. 方法 不同浓度的曲格列酮作用于GH3细胞,用MTT法检测各组GH3细胞生长情况,用流式细胞技术检测各组GH3细胞周期的变化,用半定量RT-PCR方法 检测各组GH3细胞CyclinD1基因mRNA的表达.结果 曲格列酮干预GH3细胞72 h后.以浓度效应关系抑制GH3细胞增殖,并使GH3细胞明显被阻滞于G1/S检测点,CyclinD1 mRNA表达明显减少,与对照组比较差异有统计学意义(P<0.05). 结论 曲格列酮能明显抑制大鼠垂体腺瘤细胞的增殖,其分子机制可能是其与PPAR-γ结合后导致CyclinD1 mRNA表达减少,从而抑制了细胞增殖,促进肿瘤细胞死亡.     

罗格列酮抑制垂体腺瘤GH3细胞及促凋亡作用的研究

目的探讨罗格列酮对GH3细胞增殖的影响及其促细胞凋亡的机制。方法不同浓度罗格列酮作用GH3细胞后,流式细胞仪检测细胞周期和细胞凋亡,Elisa法分析罗格列酮对生长激素合成的影响,Western blot法分析GH3细胞Cyclin D3、bcl-2和bax的变化。结果罗格列酮作用GH3细胞48 h后,以浓度效应关系抑制GH3细胞增殖、并使细胞增殖周期中G0-G1期阻滞,S期和G2-M期百分率降低;Western blot法示罗格列酮作用GH3细胞提高了Cyclin D3和bax的表达,而bcl-2的表达降低。结论罗格列酮促GH3细胞凋亡并抑制GH分泌,可能成为垂体生长激素腺瘤病人新的治疗方法。     

17β-雌二醇对垂体腺瘤GH3细胞增殖作用的实验研究

雌激素可能在泌乳素腺瘤的发生中起重要作用[1 ] 。本实验用不同浓度 17β-雌二醇 (E2 )作用于垂体腺瘤GH3细胞株 ,探讨E2与GH3细胞增殖的关系 ,建立E2对GH3细胞增殖活性检测平台 ,为筛选有效治疗泌乳素腺瘤的抗雌激素药物奠定基础。1　资料1 1　细胞培养[2 ] :GH3大鼠垂体腺瘤细胞株引自中国医学科学院基础所细胞中心 (由美国ATCC建株 )。E2 (Sigma)设 10 - 9～10 - 1 4mol/L 6个浓度 ,每个浓度设两个复孔 ,同时设溶媒对照孔(0 0 1%乙醇 )。在一组不同浓度的E2中同时加入 1μmol/L非选择性完全雌激素受体拮抗剂ICI182 780 (ICI…     

α-干扰素和溴隐亭对垂体生长激素腺瘤细胞的作用

目的研究α-干扰素(IFN-α)和溴隐亭(BC)对人垂体腺瘤细胞激素分泌的影响。方法将垂体生长激素(GH)腺瘤(11例)进行体外细胞培养,每例培养细胞随机分成IFN-α组、BC组、IFN-α BC组及对照组,每组3管,观测药物干预后细胞激素分泌量。结果干预2d和4d时,IFN-α对6/10例和7/10例垂体腺瘤细胞GH分泌有明显抑制,与对照组比较GH分泌量减少22%～54%(P<0.05或P<0.01)和30%～61%(P<0.01),其中,4/6例和5/6例侵袭性垂体腺瘤细胞GH分泌受到明显抑制,与对照组比较GH分泌量减少22%～38%(P<0.05或P<0.01)和30%～55%(P<0.01);BC对5/10例垂体腺瘤细胞GH分泌无明显抑制作用,而IFN-α对其中4例有明显抑制GH分泌效应,与对照组比较GH分泌量减少22%～54%(P<0.05或P<0.01)和30%～61%(P<0.01)。结论IFN-α对大多数垂体GH腺瘤,尤其是侵袭性垂体腺瘤细胞GH分泌有抑制作用,对大多数BC耐药的垂体腺瘤细胞GH分泌亦有抑制效应。     

雌激素受体拮抗剂对垂体腺瘤GH3细胞增殖、凋亡、催乳素分泌及雌激素受体蛋白表达的影响

目的 通过检测雌激素受体拮抗剂对垂体腺瘤GH3细胞增殖、凋亡、催乳素(PRL)分泌及雌激素受体蛋白表达的影响,探讨雌激素在垂体催乳素腺瘤发生、发展中的作用机制.方法 对去激素培养条件及加入外源性E2培养条件下的GH3细胞采用不同方法进行检测:应用MTT 法检测OHTam与ICI对GH3细胞增殖的影响;ELISA法检测对GH3细胞PRL分泌的影响;流式细胞仪测定细胞凋亡率;Western blot检测对GH3细胞ERα、ERβ表达的影响.结果 E2对GH3细胞增殖有显著的生长刺激作用,低浓度E2(10-12mol/L)即显著高于去激素培养组;OHTam与ICI对GH3细胞增殖有抑制作用,当给药浓度达到10 -6mol/L时,增殖指数分别为0.62和0.47,呈剂量依赖性;OHTam与ICI可抑制E2对GH3细胞的生长刺激作用;以上结果与对照组相比差异有统计学意义(P＜0.05).E2可促进GH3细胞的PRL的分泌,随着E2浓度的增高,PRL的分泌增加;OHTam与ICI可抑制GH3细胞PRL的分泌,并且能够抑制E2的促进作用.OHTam与ICI能够诱导GH3细胞凋亡,以早期凋亡为主.GH3细胞有ERα与ERβ的表达,E2可上调ERβ的表达水平,ICI可下调ERα的表达水平,而OHTam对ERα与ERβ的表达水平无显著影响.结论 雌激素受体拮抗剂是通过抑制细胞增殖、PRL分泌及抗雌激素而发挥抑瘤作用,而ICI的作用还与下调ERα的表达有关.     

α-干扰素和奥曲肽对垂体生长激素腺瘤的作用

目的　研究α 干扰素 (IFN α)和奥曲肽 (SMS)对人垂体腺瘤细胞激素分泌的影响。方法　将垂体生长激素 (GH)腺瘤 (11例 )标本进行体外细胞培养 ,每例培养细胞随机分成IFN α组、SMS组、IFN α +SMS组及对照组 ,每组 3管 ,观测药物干预后细胞激素分泌量的变化。结果　干预 2天和 4天时 ,IFN α对 6 0 % (6 /10例 )和 70 % (7/10例 )垂体腺瘤细胞GH分泌有明显抑制 ,与对照组比较GH分泌量减少 2 2 %～ 5 4 %和 30 %～ 6 1% (P <0 .0 5和P <0 .0 1) ,其中 ,6 7% (4/6例 )和 83% (5 /6例 )侵袭性垂体腺瘤细胞GH分泌受到明显抑制 ,与对照组比较GH分泌量减少 2 2 %～ 38%和 30 %～ 5 5 % (P <0 .0 5和P <0 .0 1) ;SMS对 4 0 % (4/10例 )垂体腺瘤细胞GH分泌无明显抑制作用 ,而IFN α对其中 3例有明显抑制GH分泌效应 ,与对照组比较GH分泌量减少 38%～ 5 4 %和 4 3%～ 6 1% (均P <0 .0 1)。结论　IFN α对大多数垂体GH腺瘤 ,尤其是侵袭性垂体腺瘤激素分泌有抑制作用 ,对大多数SMS耐药的垂体腺瘤细胞GH分泌亦有抑制效应     

细胞周期素依赖性蛋白激酶5在垂体腺瘤中的表达及其与血管内皮生长因子关系的研究

目的研究垂体腺瘤中细胞周期素依赖性蛋白激酶5 (cyclin-dependent kinase 5,CDK5)在垂体腺瘤中的表达,及其与血管内皮生长因子(vascular endothelial growth factor,VEGF)的关系。方法收集8例液氮冻存的垂体腺瘤标本作为垂体腺瘤组,4例正常垂体组织标本作为正常垂体组。应用免疫组织化学染色检测样本中p-CDK5和P35蛋白表达,Western blot检测不同浓度CDK5抑制剂Roscovitine和CDK5 si RNA对GH3细胞系中VEGF表达的影响。结果与正常垂体组比较,垂体腺瘤组VEGF和P35 m RNA表达明显增加(P 0.05),p-CDK5和P35蛋白表达亦增加。随着Roscovitine剂量增加,GH3细胞系中VEGF的表达呈递减趋势;经CDK5 si RNA处理后,VEGF表达降低。结论垂体腺瘤中CDK5的活性明显增加,抑制CDK5活性可降低垂体腺瘤中VEGF的表达。     

Pituitary abscess

Pituitary abscess is a rare disease, but one with potentially high mortality and morbidity. We present a 46-year-old man with progressive visual disturbance and general malaise for 1 year. Endocrine studies revealed hypopituitarism, and magnetic resonance imaging revealed a pituitary lesion with suprasellar extension. We attempted to excise the lesion using a transsphenoidal approach, but pus in the pituitary fossa was found at operation, and no tumour was identified. The culture yielded coagulase-negative Staphylococcus. Antibiotics were administered for 3 weeks, and the patient made a good postoperative recovery. He required life-long hormone replacement therapy. After one and a half years of follow-up, he was well and had no evidence of focal or systemic infection. We review the literature regarding pituitary abscess and discuss the appropriate treatment and possible pathological mechanism.     

35例急性垂体瘤卒中的临床分析

急性垂体瘤卒中是一种危急状态,它往往表现为突发头痛、恶心、眼肌麻痹、视力视野的急剧下降,严重者可因垂体功能不足而危及生命。本科自1996至2004年共收治了35例急性垂体瘤卒中患者,现将其临床表现、影像学资料、预后等作回顾性分析,并探讨提高急性垂体瘤卒中诊断、治疗的方法。     

Pituitary Apoplexy due to Pituitary Adenoma Infarction

Cause of pituitary apoplexy has been known as hemorrhage, hemorrhagic infarction or infarction of pituitary adenoma or adjacent tissues of pituitary gland. However, pituitary apoplexy caused by pure infarction of pituitary adenoma has been rarely reported. Here, we present the two cases pituitary apoplexies caused by pituitary adenoma infarction that were confirmed by transsphenoidal approach (TSA) and pathologic reports. Pathologic report of first case revealed total tumor infarction of a nonfunctioning pituitary macroadenoma and second case partial tumor infarction of ACTH secreting pituitary macroadenoma. Patients with pituitary apoplexy which was caused by pituitary adenoma infarction unrelated to hemorrhage or hemorrhagic infarction showed good response to TSA treatment. Further study on the predisposing factors of pituitary apoplexy and the mechanism of infarction in pituitary adenoma is necessary.     

垂体瘤卒中诊断和治疗的再探讨

目的探讨典型和不典型垂体瘤卒中的发病机制,从而为合理制定治疗方案和正确选择手术时机提供帮助。方法经临床表现和/或手术治疗及病理学诊断为垂体瘤卒中病例28例中,24例符合垂体瘤卒中的典型临床表现,另4例符合不典型垂体瘤卒中的诊断。分析垂体瘤卒中的临床表现、影像学表现、手术及病理发现与病程之间的关系及其在病程中各时期的影像学表现、手术发现及病理诊断的特征。结果根据典型垂体瘤卒中病程中不同阶段的临床症状体征、影像学、手术及病理特点,将病程分为早期梗死出血期和后期坏死期,手术全切率分别为87.5%(7/8)和100%(14/14)。不典型垂体瘤卒中的影像学、手术和病理均证实为瘤内陈旧性出血,手术全切率为75.0%(3/4)。结论典型垂体瘤卒中多因肿瘤梗塞后坏死并继发出血所致,急诊手术治疗目的是为了缓解症状。后期坏死期的手术效果明显优于早期梗死出血期,症状不显著者可采用激素替代保守治疗。不典型垂体瘤卒中以慢性瘤内出血为主要特征,无急诊手术治疗指征。     

巨大垂体腺瘤切除术中的垂体柄保护及意义

目的 探讨巨大型垂体腺瘤切除手术中的垂体柄保护。方法 采用经纵裂蝶窦入路显微手术切除巨大型垂体腺瘤52例。结果 肿瘤全切除39例（75％）。垂体柄保留34例（65％）。术后发生尿崩32例（62％），其中23例在术后1－2周内恢复正常，占术后尿崩总数的72％；7例在3个月内恢复；2例尿崩症状持续1年以上。结论 垂体腺瘤手术中的垂体柄保留可有效降低术后尿崩症，特别是永久性尿崩症的发生，是提高手术效果的重要措施。     

垂体瘤患者手术前后垂体功能评估情况调查分析

目的分析垂体瘤患者术前、术后1周及3个月的垂体功能情况,探讨垂体瘤患者的综合治疗水平。方法收集2012-01—2016-12我院收治的垂体瘤患者236例,回顾性分析术前及术后临床资料。结果术前垂体功能评估率较低,为16.53%,术前评估垂体功能者存在垂体功能减退者占60.98%。术后1周的垂体功能评估率为24.64%,术后3个月的垂体功能评估率为10.54%,术后1周评估垂体功能减退率为45.10%,术后3个月的垂体功能减退率为50.00%。术前及术后垂体瘤患者均未得到更多的垂体功能评价。结论垂体瘤患者术前及术后垂体功能评估率较低,术前缺少评估可能会增加患者的手术风险,高估术后垂体功能减退的发生率。垂体瘤术后垂体功能减退的患者存在较多漏诊。     

Pituitary metastasis: From pathology to clinical and radiological considerations

PurposeA review of the literature with respect to pituitary metastases (PM) with clinical and radiological considerations are summarized to facilitate clinical decision making in the management of PMMethodsA review of literature associated with PM and tumour to tumour metastases in the English literature was reviewed and summarizedResultsPituitary metastases account for 1.0–3.6% of all surgically treated pituitary lesions. Often identified in parallel with extensive disseminated disease, once diagnosed, the prognosis is generally poor, although survival is highly heterogeneous and dependent on the primary tumor histology. Within this anatomical region is also the observation of tumor-to-tumor metastases and collision tumours. Both the tumor macro- and microenvironment play central roles to the progression of disease with distinctive radiological features that may suggest a metastatic sellar lesion as opposed to a primary pituitary lesion. Surgical resection is the first line of therapy followed by adjuvant chemoradiotherapy and endocrinological evaluation for hormonal supplementationConclusionPMs are relatively rare but important oncological entities representing disseminated disease in the majority of cases. Careful consideration of the relevant clinical history and radiological features can aid the clinician differentiate between a metastatic lesion to the pituitary region and a primary pituitary tumor. While surgical resection is first line therapy, stereotactic radiosurgery in carefully selected patients is emerging as a viable alternative.     

原发性甲状腺功能减退致垂体增生四例报告及文献复习

目的 探讨原发性甲状腺功能减退致垂体增生的诊断和处理原则.方法 结合文献回顾性分析4例原发性甲状腺功能减退致垂体增生的临床资料.结果 4例均表现为促甲状腺激素(TSH)及催乳素(PRL)增高,FT3及FT4减少,MRI示垂体增大,甲状腺素替代治疗2-4个月后,垂体恢复正常,TSH及PRL水平亦恢复正常.结论 原发性甲状腺功能减退致垂体增生具有影像学特征,结合临床可明确诊断.治疗首选甲状腺素实验性替代治疗,而不宜行手术治疗.     

Radiological Apoplexy and Its Correlation with Acute Clinical Presentation, Angiogenesis and Tumor Microvascular Density in Pituitary Adenomas

Objective

Pituitary apoplexy is life-threatening clinical syndrome caused by the rapid enlargement of a pituitary tumor due to hemorrhage and/or infarction. The pathogenesis of pituitary apoplexy is not completely understood. We analyzed the magnetic resonance imaging (MRI) of pituitary tumors and subsequently correlated the radiological findings with the clinical presentation. Additionally, immunohistochemistry was also performed to determine whether certain biomarkers are related to radiological apoplexy.

Methods

Thirty-four cases of pituitary adenoma were enrolled for retrospective analysis. In this study, the radiological apoplexy was defined as cases where hemorrhage, infarction or cysts were identified on MRI. Acute clinical presentation was defined as the presence of any of the following symptoms: severe sudden onset headache, decreased visual acuity and/or visual field deficit, and acute mental status changes. Angiogenesis was quantified by immunohistochemical expression of fetal liver kinase 1 (Flk-1), neuropilin (NRP) and vascular endothelial growth factor (VEGF) expression, while microvascular density (MVD) was assessed using Endoglin and CD31.

Results

Clinically, fourteen patients presented with acute symptoms and 20 for mild or none clinical symptoms. Radiologically, fifteen patients met the criteria for radiological apoplexy. Of the fifteen patients with radiologic apoplexy, 9 patients presented acute symptoms whereas of the 19 patient without radiologic apoplexy, 5 patients presented acute symptoms. Of the five biomarkers tracked, only VEGF was found to be positively correlated with both radiological and nonradiological apoplexy.

Conclusion

While pituitary apoplexy is currently defined in cases where clinical symptoms can be histologically confirmed, we contend that cases of radiologically identified pituitary hemorrhages that present with mild or no symptoms should be designated subacute or subclinical apoplexy. VEGF is believed to have a positive correlation with pituitary hemorrhage. Considering the high rate of symptomatic or asymptomatic pituitary tumor hemorrhage, additional studies are needed to detect predictors of the pituitary hemorrhage.     

垂体腺瘤患者血浆神经肽Y与垂体激素水平相关性研究

目的 探讨垂体腺瘤患者血浆神经肽Y（NPY）与垂体激素之间的相关关系。方法 收集82例垂体腺瘤患者及20例对照组空腹静脉血3ml，进行血浆NPY放免测定分析，并与垂体激素水平进行相关分析。初步探讨NPY与部分其他临床指标之间的相关性。结果 （1）垂体腺瘤患者、泌乳素细胞腺瘤、生长激素细胞腺瘤、无内分泌功能细胞腺瘤及多分泌功能细胞腺瘤组中血浆NPY与PRL呈负相关。（2）垂体腺瘤患者血浆NPY与ACTH呈正相关。（3）促性腺激素细胞腺瘤中NPY与LH呈正相关而与GH呈负相关。（4）NPY在垂体腺瘤组与对照组中血浆含量明显不同，而且部分不同垂体腺瘤组之间也存在明显差异。（5）全组垂体腺瘤手术后血浆NPY的含量下降。结论 NPY参与了垂体腺瘤病理生理中下丘脑-垂体轴许多激素的调节，可能与垂体腺瘤的发生有关。