垂体泌乳素分泌腺瘤细胞体外培养和激素分泌的研究

为研究垂体泌乳素(PRL)腺瘤体外细胞培养及激素分泌的特征,选择经临床、手术和病理证实的7例垂体PRL腺瘤和3例PRL/GH混合性腺瘤,采用细胞培养技术,观察细胞形态的改变和生长的特点,观测培养基基础激素分泌量随时间的改变.结果显示10例垂体腺瘤细胞培养成功8例,成活率为80%,贴壁后的细胞被拉长,呈椭圆形或梭形,呈团状或片状生长,培养基中PRL分泌量在1周内维持较高水平,1周后缓慢下降,而GH分泌量呈现迅速下降的趋势.提示培养基中高PRL水平预示着肿瘤的早期复发.     

TRH、GRH及溴隐亭对垂体生长激素腺瘤细胞分泌激素的影响

对６例生长激素（ＧＨ）腺瘤患者手术前后分别进行促甲状腺激素释放激素（ＴＲＨ）兴奋试验。手术切除后的ＧＨ腺瘤组织用于体外细胞培养，在细胞培养液中分别掺入ＴＲＨ、生长激素释放激素（ＧＲＨ）及溴隐亭（ＢＲＥ），观察在短时间内激素或药物对培养细胞分泌ＧＨ及泌乳素（ＰＲＬ）的影响。结果：ＧＨ腺瘤细胞对ＴＲＨ的作用反应异常，瘤细胞的某些特性与正常垂体ＧＨ细胞相比差异甚大。ＴＲＨ兴奋试验可作为ＧＨ腺瘤患者术后病情判断及估计预后的良好参考。ＧＲＨ对多数病例的ＧＨ腺瘤细胞有促进分泌ＧＨ的作用，其反应敏感性与肿瘤组织块的大小有明显关系。ＢＲＥ直接作用于ＧＨ腺瘤细胞，能抑制细胞分泌ＧＨ，但个体差异较大。ＴＲＨ和ＧＲＨ各自对ＧＨ－ＰＲＬ混合性腺瘤的作用特点对鉴别腺瘤组织的不同细胞构成有所帮助。     

Galanin协同生长释放素（GHRH）促进生长激素（GH）的释放

Galanin是新发现的促进GH释放的下丘脑激素。已知给正常人反复注射GHRH会导致GH释放的减低。我们研究了6例正常人对重复注射GHRH同时滴注galanin的GH反应。结果表明重复注射GHRH后GH释放明显减低,但在重复注射同时合用galanin则GH释放显著增强。galanin和GHRH联合应用克服了因重复注射GHRH所致的GH反应降低。其机理可能是gatanin抑制下丘脑SRIH的分泌之故。     

Relationship between GHRP-6 and TPA in the Regulation ofGrowth Hormone Secretion by Human PituitarySomatotrophinomas

Growthhormonereleasing-peptide(GHRP--6)isasyntheticpeptidewhichspecificallystimulatessecretionofgrowthhormone(GH)bypituitarysomatotrophs.ManyevidencesshowedthatGHRP--6mediateditseffectsmainlyviahydrolysisofmembranephosphatidylinositol(PI)intoinositol--1,4,5--trisphosphate(lP,)anddiacylglycerol(DAG)andthesubsequentactivationofproteinkinaseC(PKC)[2'3-5'7,sj.Phorbolester,l,2tetradecanoylphorbol13acetate(TPA),stimulatesGHsecretionviaPKC[s.s].Inordertounderstandtheirprecisemechanisms,wei…     

吡啶斯的明对生长激素分泌及其释放激素的激发与增效作用

观察了吡啶斯的明(PD)对正常儿童、垂体性和下丘脑性生长激素(GH)缺乏病儿GH分泌的激发作用和对生长激素释放激素(GHRH)的增效作用。结果表明,PD有良好的激发GH分泌作用,可作为GH缺乏的筛选试验。PD对正常儿童和下丘脑性GH缺乏病儿有明显的增加GHRH引起的GH释放效应。PD可能对某些GH缺乏病儿及其他原因所致的身材矮小病儿有较好的治疗效果。     

急性颅脑外伤垂体前叶激素的动态变化及其临床意义

对24例开颅手术的急性颅脑外伤患者的血清卵泡刺激素、黄体生成激素、促甲状腺激素、三碘甲状腺原氨酸、甲状腺素、生长激素和催乳素在伤后10d内作了动态观察。结果显示，脑外伤后垂体和甲状腺功能有明显变化，变化程度与颅脑外伤的严重程度有关。我们认为，测定颅脑外伤后垂体和甲状腺功能，并作动态观察，有助于判断脑外伤程度和估计预后。     

低生长激素性巨人症

报告 1例低生长激素水平且垂体大小正常的巨人症。患者 ,女 ,11岁 ,因生长过速 6年入院。查体 :身高 181cm,体重 77kg,指间距 187cm。骨龄 11.1岁 ,血清基础生长激素水平小于 1ng/ml,血清 T3 、T4、FT3 、FT4、TSH、E2 、L H、FSH、PRL、PTC及血浆 ACTH水平正常。胰岛素低血糖刺激试验、精氨酸刺激试验显示生长激素无反应。双手及头颅 X片显示尺、桡骨、掌指骨粗大 ,双手指骨骨皮质变薄 ,指骨增长 ,颅骨增大 ,颅板增厚 ,枕骨粗隆呈倒钩状。心三位片显示左、右心室轻度增大。头颅 MRI显示垂体大小正常 ,无异常信号。对于该例患者 ,非脉冲式的 GH分泌和组织对 GH敏感性增加也许导致 IGF- 1过度分泌 ,以及未分类的促生长因子和具生物活性的抗生长激素受体抗体的存在可能是导致临床上出现巨人症的原因     

多巴胺和溴隐亭对体外垂体生长激素瘤细胞分泌生长激素的影响

本实验研究多巴胺(DA)及其激动剂溴隐亭(CB154)对6例体外培养的垂体单纯生长激素(GH)分泌瘤GH分泌的调节作用,并与生长抑素类似物SMS_(201-995)(SMS)的作用进行比较。结果10~(-8)和10~(-7)mol/LDA仅使1例瘤细胞的GH分泌明显减少,分别下降到对照GH分泌量的50.6％和44.4％;而10~(-7)和10~(-6)mol/L CB154却能使4例瘤细胞中3例GH分泌明显减少,平均下降到59.0±8.9％,表明CB154抑制GH分泌的作用强于DA。10~(-6)mol/L CB154使GH分泌下降到63.3±13.8％,而10~(-7)mol/L SMS则可使GH分泌下降到45.5±13.1％,二者浓度相差10倍,提示SMS的抑制作用至少比CB154强10倍。CB154不但能抑制GH分泌,还能抑制GH合成;而SMS则主要抑制GH分泌,对GH合成无明显影响。以上结果提示DA和CB154可直接抑制部分单纯GH分泌瘤GH的分泌,其作用机理与SMS不完全相同。     

生长激素治疗对GHD患儿免疫功能的影响

对生长激素缺乏症（GHD）患儿生长激素（GH）治疗前后的免疫功能改变进行了观察。结果显示：（1）GHD患儿NK细胞活性明显降低，经GH治疗3个月后恢复到正常水平；（2）GHD患儿治疗前IL－1a和IL－2活性偏低，治疗后两者有逐渐增高的趋势；（3）治疗前后CD细胞亚群、sIL－2R和LPS诱生的TNFa含量均无明显变化。认为GH缺乏症患儿存在一定的免疫功能缺陷，而GH有调节其免疫功能的作用。     

生长激素释放多肽通过与生长激素释放因子不同的受体起作用

用固相法合成了生长激素释放因子(GRF),生长激素释放多肤(GHRP)和生长激素释放抑制因子(GRF-AN,D-Arg2-GRF44),并检测了多肽的生物学活性。结果表明1.GRF和GHRP在体内外均可刺激人垂体生长激素(GH)分泌。2.GRF和GHRP体外灌流时均可刺激牛垂体GH分泌。3.GHRP可促进大鼠生长发育。4.GRF-AN可抑制由GRF兴奋的人和动物垂体GH释放,但有较强的选择性,GRF-AN不抑制由GHRP兴奋的GH释放。表明,GRF和GHRP均可兴奋垂体GH分泌,但二者的机制有本质上的区别。     

THE ROLE OF CALCIUM ION IN THE PATHOGENESIS OF HUMAN PITUITARY GH－SECRETING ADENOMAS

ＴＨＥＲＯＬＥＯＦＣＡＬＣＩＵＭＩＯＮＩＮＴＨＥＰＡＴＨＯＧＥＮＥＳＩＳＯＦＨＵＭＡＮＰＩＴＵＩＴＡＲＹＧＨ－ＳＥＣＲＥＴＩＮＧＡＤＥＮＯＭＡＳＤｅｎｇＪｉｅｙｉｎｇ（邓洁英）；ＳｈｉＹｉｆａｎ（史轶蘩）ａｎｄＹｉｎＪｕａｎＪｕａｎ（尹娟娟）（Ｄｅｐ...     

TPA enhances growth hormone (GH) secretion effect of GH-releasing hormone (GHRH) by human gsp-positive pituitary somatotrophinomas

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Growth hormone, prolactin and thyrotrophin responses to thyrotrophin-releasing hormone in diabetic patients.

Growth hormone (GH), prolactin (PRL) and thyrotrophin (TSH) responses to thyrotrophin-releasing hormone (TRH) were studied in 15 insulin-dependent diabetic patients. Basal plasma GH levels were raised above 5 mu./l in 6 patients and following the injection of TRH there was a significant rise in plasma GH levels in 9. The mean rise in plasma GH from basal to peak values was significant in the group as a whole (P < 0.01). Basal PRL and TSH levels were normal and rose normally in response to TRH. GH release may be qualitatively abnormal in some diabetics and any such loss of specificity of GH-releasing mechanisms would further contribute to the raised GH levels found in many diabetics which would be of importance if GH is a factor in the aetiology of diabetic microangiopathy.     

垂体瘤手术对内分泌激素的影响

为了解垂体瘤手术对垂体激素分泌的影响,动态观察了１５０例垂体瘤患者在显微外科手术前后血清泌乳素（ＰＲＬ）、生长激素（ＧＨ）、甲状腺功能〔Ｔ３、Ｔ４、促甲状腺素（ＴＳＨ）〕、血皮质醇（Ｆ）和促肾上腺皮质激素（ＡＣＴＨ）的变化。结果：术后１周内ＰＲＬ、ＧＨ水平明显下降且与以后的ＰＲＬ、ＧＨ水平基本一致,故认为术后１周的ＰＲＬ、ＧＨ水平可做为判断手术疗效的主要指标之一;所有垂体瘤患者Ｔ３术后较术前均显著降低,提示手术摘除垂体腺瘤可引起Ｔ３水平的下降,而其他激素水平无明显变化。     

内分泌激素水平监测对生长激素型垂体腺瘤患者手术远期疗效的观察

目的 探讨内分泌激素水平监测对生长激素型垂体腺瘤患者手术远期疗效观察的意义.方法 动态观察2002至2009年在青岛大学医学院附属医院经显微外科手术治疗的38例生长激素型垂体腺瘤患者手术前后血清生长激素、泌乳素、甲状腺激素(T3、T4)、促甲状腺素(TSH)、血皮质醇(COR)和促肾上腺皮质激素(ACTH)的变化,并进行1年以上的随访和远期疗效评价.结果 生长激素垂体腺瘤全切患者22例,术后1周内生长激素水平明显下降[术后1周与术前分别为(2.49±0.22)μg/L和(9.24±0.56)μg/L,P＜0.05]且与以后的生长激素水平基本一致.术后1周内生长激素降至2.5μg/L以下者11例,11例生长激素未降至2.5μg/L以下,其中3例术后3年内复发.结论 术后1周的生长激素水平可作为判断手术疗效的指标之一,术后1周内生长激素降至2.5μg/L以下可作为判断临床治愈的指标.

Abstract：

Objective To investigate the effect of incretion hormones on growth pituitary adenoma ectomy patients and evaluate its long-term therapeutic efficacy. Methods A total of 38 growth pituitary adenoma patients were treated by adenoma ectomy between 2002 to 2009 at our hospital. The dynamic concentrations of serum prolactin (PRL), growth hormone (GH), cortisone, adrenocorticotrophic hormone (ACTH) and thyroid function (T3, T4 & thyroid-stimulating hormone) were monitored before and after microsurgery. All cases had been followed up for over one year to evaluate the long-term therapeutic efficacy.Results The level of GH decreased markedly within one week after ectomy [(2. 49 ± 0. 22 ) μg/L vs (9. 24 ±0. 56) μg/L,P ＜0. 05]and remained stable afterwards. Among 22 cases of GH-secreting pituitary adenoma with total removal, the post-operative level of GH dropped below 2. 5 μg/L in 11 cases but the other 11 cases did not. And 3 cases were recurrent within 3 years post-operation. Conclusions The GH level at Week 1 post-operation is one of the major indicators for evaluating the efficacy of surgery. And the level of GH dropping below 2. 5 μg/L at Week 1 post-operation may be used as a standard for clinical cure.     

INHIBITORY EFFECTS OF ATROPINE ON GROWTH HORMONE RELEASE IN NORMAL SUBJECTS AND ACROMEGALY

Growth hormone (GH) secretion is mediated by hypothalamic factors, mainly growth hormone releasing factor (GRF) and somatostatin (SS). The hypothalamic hormones, under direct neurotransmitter control, stimulate GH secretion through different central mechanisms. Atropine, an anticholinergic agent, can cross the blood-brain barrier and inhibit GH secretion stimulated by exercise and sleep in normal persons. In order to study the inhibiting effect of atropine on GH release and whether glucose can be replaced by atropine, normal persons and acromegaly patients were observed during exercise, after atropine, and 100 g glucose loading. The results confirmed that GH secretion increases after exercise and that this GH elevation can be inhibited by atropine in normal subjects. But in acromegaly patients high basal GH levels can not be inhibited by 100 g glucose loading or 0.6 mg atropine during the active phase of the disease. Blood sugar levels remained unchanged during the atropine test. It is suggested that the atropine test can be used as a GH inhibitory test in acromegaly patients with overt diabetes.     

严重急性呼吸综合征患者腺垂体GH、PRL细胞免疫组织化学研究

目的通过研究严重急性呼吸综合征（SARS）患者腺垂体远侧部嗜酸性细胞所含激素的变化,探讨SARS发病过程中内分泌与疾病的关系。方法对4例SARS患者的尸体解剖腺垂体远侧部组织进行石蜡切片,免疫组织化学染色,观察生长激素（growth hormone,GH）和催乳激素（prolactin,PRL）阳性细胞的变化。结果与对照组相比患者腺垂体远侧部的GH细胞免疫反应强度显著降低（P〈0.01）,而PRL细胞免疫反应强度显著增强（P〈0.01）。结论 SARS患者的腺垂体远侧部GH、PRL细胞免疫组织化学染色结果异常,细胞的激素合成功能受到影响。     

Clinical and biochemical characteristics of growth hormone-secreting pituitary tumors

It has been confirmed that gsp oncogene is oneof the main cause of growth- hormone secreting pitu-itary tumor in native acromegaly patients[1] ,but dif-ference in clinical and biochemical characteristics be-tween gsp- positive and gsp- negative patients re-mained unknown. We selected 1 8cases of growthhormone( GH) - secreting pituitary tumors to studytheir clinical and biochemical characteristics.All pa-tients also underwent pituitary function combinativestimulating testto evaluate the pituita…     

垂体特异转录因子pit-1在垂体瘤中的表达及意义的实验研究

目的 检测垂体特异转录因子pit-1在垂体腺瘤中的表达，研究Pit-1与激素水平、肿瘤侵袭性的关系。以探讨Pit-1在垂体瘤发病机制中的作用。方法 根据术前激素水平、临床表现及术后病理诊断确定腺瘤类型，依影像学表现、术中所见及硬膜病检结果判断对肿瘤侵袭性分级，用免疫组化和RT-PCR分别测定Pit-1蛋白和pit-1mRNA的表达。结果 Pit-1在GH腺瘤、PRL腺瘤、GH／PRL混合腺瘤中均有表达。与对照组相比，中、高度表达者占此3种腺瘤的78．8％（26／33），无功能腺瘤及ACTH腺瘤中无Pit-1蛋白的表达。pit-1mRNA在全部的GH腺瘤、PRL腺瘤、GH／PRL混合腺瘤和50％（5／10）的无功能腺瘤中有表达，在ACTH腺瘤组中无表达。GH、PRL、GH／PRL混合腺瘤组间pit-1mRNA的表达量差异无显著性，此3组均显著高于无功能腺瘤组（P〈0．05）。GH、PRL腺瘤组中pit-1mRNA的表达量与其各自术前的激素水平呈显著正相关。在表达pit-1mRNA的腺瘤中，侵袭性组高于非侵袭性组。结论 Pit-1的表达与垂体腺瘤的表型、功能有关，与某些激素（GH、PRL）水平、肿瘤的侵袭性呈正相关，在某些类型（GH、PRL、GH／PRL）的垂体瘤发病机制中起重要作用。     

立体定向伽玛刀治疗功能性垂体腺瘤

目的:探讨对伽玛刀治疗功能性垂体腺瘤的疗效及相关因素。方法:回顾性分析伽玛刀治疗的412例功能性垂体腺瘤患者的临床资料。其中207例为PRL型,89例GH型,46例为ACTH,70例为混合型;肿瘤所接受的平均边缘剂量分别为30.6Gy、22.1Gy、34.5Gy、和21.7Gy。结果:平均随访时间为24个月,90例(40.2%)内分泌恢复正常,119例(53.1%)下降,无变化或升高15例(6.7%),84例肿瘤消失,117例(52.2%)肿瘤缩小,1例(0.4%)增大。结论:伽玛刀治疗功能性垂体腺瘤是安全有效的方法,不仅能控制肿瘤生长,而且能使内分泌功能大部分恢复正常。