生长激素释放激素兴奋试验

生长激素释放激素(GHRH)是下丘脑分泌的兴奋垂体生长激素(GH)细胞分泌GH的激素。1982年Guillemin及Rivier等分别自引起肢端肥大症的胰腺肿瘤组织中分离提纯了三种GHRH,其氨基酸数目分别为44、40及37。实验证明GHRH C末端1～29个氨基酸是生物活性所必需的。人下丘脑分泌的GHRH与胰腺肿瘤组织中提出的GHRH有相同的免疫及生物活性,可特异地兴奋GH分泌,对其他垂体前叶激素无刺激分泌的作用。近来已确定     

生长激素释放激素和生长抑素对垂体生长激素细胞的作用

早在六十年代,人们已觉察到下丘脑对垂体前叶生长激素(GH)的分泌有兴奋性和抑制性两种作用,但直到1973和1982年,美国的Guillemin及其同事才分别将生长抑素(SS)和生长激素释放激素(GHRH)分离、提纯,并阐明其结构。从此,GHRH和SS对垂体GH细胞调节的研究进入到细胞水平以至分子水平,这些研究大大推动了内分泌生理学和病理生理学的发展。现就最近几年关于GHRH和SS对垂体GH细胞的生理作用及细胞内机制作一简要综述。     

垂体生长激素的调节激素对人B淋巴母细胞系IM-9中生长激素基因启动子活性的影响

目的：通过观察生长激素释放激素（GHRH）、山德定、生长激素（GH）和胰岛素样生长因子I（IGF－I）对IM－9细胞中GH基因启动子活性的影响，以了解这些激素对B淋巴细胞中GH表达的调节作用。方法：把人外周血淋巴细胞GH基因上游－484～ 2bp调控序列克隆到荧光素酶报告基因质粒中，然后把克隆得到的质粒转染到IM－9细胞内，通过测量荧光素酶泊活性观察垂体GH的各种调节激素对GH基因启动子活性的影响。结果：0．001nmol/L的人GHRH能够显著抑制荧光素酶在IM－9细胞中的表达（P＜0．002），但0．1nmol/L和10nmol/L的GHRH对荧光素酶的抑制作用反而减弱。人IGF－I（1、10和100nmol/L可增强荧光素酶的表达（均P＜0．05）。GH（1．0ng/ml）可显著增加荧光素酶的表达，但作用的强度不大。不同浓度的生长抑素类似物山德定对IM－9细胞中荧光素酶的表达均无显著影响。结论：GHRH、IGF－I和GH对IM－9细胞中GH启动子的活性有一定的调节作用,说明调节垂体GH分泌的GHRH、IGF－I和GH等能够调节G淋巴细胞内irGH的表达。     

“交叉通讯”在人垂体生长激素腺瘤激素分泌中的调控作用研究

目的:探讨在人垂体生长激素腺瘤中,细胞内信号的交叉通讯对生长激素分泌的调控作用。方法:采用体外垂体生长激素(GH)腺瘤细胞培养方法,观察在生长激素释放激素(GHRH)和人工合成的GH释放肽(GHRP-6)刺激下,2种垂体腺瘤细胞内信号系统的交叉通讯在GH释放中的调控作用。结果:GHRH和GHRP-6对垂体腺瘤的GH分泌有协同刺激效应。cAMP、PKC在两种信号传导系统的交叉通讯中起着重要作用。结论:在垂体GH腺瘤的激素释放调控中,多种细胞内信号的“交叉通讯”有重要意义。     

检测血清IGF-1和IGFBP-3对儿童生长激素缺乏症的诊断价值

目的：探讨血清胰岛素样生长因子-1(IGF-1)和胰岛素样生长因子结合蛋白-3(IGFBP-3)浓度在诊断生长激素缺乏症(GHD)患儿中的应用价值。方法：用免疫放射分析检测38例GHD患儿和42例对照儿童的血清IGF-1和IGFBP-3,同时进行生长激素(GH)激发试验,用化学发光法检测GH,对两组结果进行比较。结果：GHD组患儿IGF-1和IGFBP-3均显著低于对照组儿童,且在GH激发试验中,GH的增加值也明显低于对照组。结论：检测血清中的IGF-1和IGFBP-3,对诊断GHD儿童具有重要价值。     

左旋多巴激发试验对儿童生长激素缺乏症的临床价值

目的:探讨左旋多巴激发试验在诊断儿童生长激素缺乏症(GHD)的临床价值。方法:对330例身材矮小儿童应用左旋多巴激发试验,采用化学发光法进行生长激素(GH)检测。以测得的GH最高值为峰值,峰值≥10ng/ml为GH不缺乏,激发试验阳性;10ng/ml>峰值≥5ng/ml为GH部分缺乏,峰值<5ng/ml为GH缺乏,激发试验阴性。结果:激发后峰值强度为(12.23±8.10)ng/ml;峰值出现在(30～90)min者占96%,出现在120min者占4%(阳性3例),两者峰值有显著性差异(P<0.01);GH完全缺乏者占21%,部分缺乏者占22%,完全不缺乏者占57%。结论:左旋多巴激发试验可应用于临床GHD的诊断,但其诊断敏感度低,需要联合其它激发方式和其它指标对GHD患者进行综合评价。     

矮小症患儿生长激素激发试验与治疗反应的相关性

目的分析生长激素缺乏症(GHD)和特发性矮小症(ISS)患者生长激素激发试验结果,及其与重组人生长激素(rhGH)治疗反应之间的关系。方法回顾性分析36例GHD和24例ISS左旋多巴和胰岛素低血糖生长激素激发试验结果,rhGH治疗后身高增长情况,进行相关性分析。结果 GHD组两种激发试验峰值、曲线下面积(area under curve, AUC)与身高标准差比值(SDS)呈正相关(P0.001),校正性别、年龄、骨龄、体质量SDS后,左旋多巴激发试验峰值及AUC与身高SDS仍呈正相关(r=0.471和0.427,P0.05);ISS组并无此相关性。两组治疗前身高SDS无差异,治疗第2年GHD组身高SDS显著高于ISS组(P0.05)。两组治疗后GV均明显增加,但治疗第2年GV较第1年有所下降。GHD组治疗第1年GV与治疗前两种激发试验峰值、AUC呈负相关,而ISS组并无相关性。结论 rhGH可显著改善GHD和ISS患儿身高,但随着治疗的延长GV有下降趋势;治疗前GH激发试验可一定程度预测GHD患儿rhGH治疗效果,但不能预测ISS患儿rhGH治疗效果。     

儿童生长激素缺乏症临床试验的综合评估(附20例临床分析)

目的评价20例生长激素缺乏症(GHD)儿童激素水平,包括生长激素(GH)、游离甲状腺素(FT3、FT4)、促甲状腺素(TSH)、促性腺激素(LH及FSH)、空腹血糖与垂体CT.方法所有内分泌激素均经放射免疫法(RIA)测定.生长激素激发试验分别给以口服左旋多巴(10mg/kg)及静脉注射胰岛素(0.05～0.1U/kg).随后,在0、30、60、90分钟分别抽血测定.空腹血糖为常规方法测定.垂体CT为冠状位增强扫描.结果20例中GH完全缺乏16例,GH部分缺乏症4例.其中2例合并中枢性甲状腺功能低下,2例合并外周性甲状腺功能低下.20例中15例促性腺激素分泌不足.垂体CT显示垂体正常7例,垂体发育不良10例,空蝶鞍3例.空腹血糖低于正常水平12例.结论生长激素缺乏症除生长激素分泌不足外,易伴发性腺及甲状腺功能受损.空腹血糖水平较易低下.提示对这类患儿应综合评估.垂体CT提示患儿垂体可有不同程度异常,不应忽视.     

6例Noonan综合征患者临床特点及重组人生长激素治疗效果分析

目的 本研究将总结6例Noonan综合征(NS)患者的临床特点、基因诊断结果及对重组人生长激素(rh GH)治疗的反应。方法 回顾性总结2009年5月至2015年8月在北京协和医院内分泌科矮小门诊的6例NS患者的临床特点。5例以0.1 IU/(kg·d)为起始剂量应用rh GH,进行定期随访,并与年龄/性别相匹配的同期应用rh GH的10例特纳综合征(TS)和10例生长激素缺乏症(GHD)患者进行比较。结果 6例患者均存在NS的典型临床表现;5例经rh GH治疗后,年生长速度显著增加(P0.01);NS与TS患者rh GH疗效相似,随访各点均无显著性差异;但GHD患者相比,在应用rh GH后疗效欠佳;不良事件:2例NS在随访期出现亚临床甲状腺功能减低。结论 NS患者具有典型的临床表现,基因检查有助于明确诊断,rh GH治疗有显著疗效及较高的安全性。     

IGF-Ⅰ、IGFBP-3诊断矮小儿童生长激素缺乏的价值

目的:探讨胰岛素样生长因子-Ⅰ ( IGF-Ⅰ)和胰岛素样生长因子结合蛋白-3 ( IGFBP-3)诊断矮小儿童生长激素缺乏的价值.方法:①对64例身材矮小患儿用精氨酸激发试验和左旋多巴激发试验检测其血清生长激素(GH)水平,两项药物激发试验GH峰值均＜10ng/ml诊断为生长激素缺乏(GHD组,40例),其中有一项激发试验GH峰值＞10ng/ml,即可确实诊断为特发性矮小症( ISS组,23例).选取45例健康儿童作为对照组.②用化学发光法检测血清IGF-Ⅰ和IGFBP-3水平.结果:①血清IGF-Ⅰ水平,GHD组为(80.35±32.46)ng/ml,ISS组为(123.26±62.13)ng/ml,正常对照组为(362.20±78.21)ng/ml;血清IGFBP-3水平,GHD组为(2.67±1.32)ng/ml,ISS组为(3.62±1.524)ng/ml,正常对照组(6.39±1.06)ng/ml.②GHD组和ISS组患儿血清IGF-Ⅰ和IGFBP-3水平显著低于健康对照组(P<0.05) ;GHD组比ISS组患儿血清IGF-Ⅰ、IGFBP-3水平减低有显著性差异(P<0.05).③按正常对照组x-2s作为临界值诊断GHD,IGF-Ⅰ的阳性率为95%; IGFBP-3的阳性率为92.5%;IGF-Ⅰ、IGFBP-3水平同时评价时,阳性率为87.50%.结论:IGF-Ⅰ、IGFBP-3检测可用于诊断身材矮小儿童的生长激素缺乏.     

健康儿童、青少年血清生长激素的参考值调查

采用放射免疫法测定286例昆明市3～18岁健康儿童及青少年血清生长激素(GH)浓度。儿童、少年期组(3～12岁 ,n=163)和青春期组(13～18岁 ,n=123)血清GH浓度(x+s)分别为3.02±2.01 ;6.98±5.05 ,用百分位数法求出双侧P2.5和P97.5的值。参考值范围儿童、少年期组0.20～12.8ng/ml,青春期组0.70～28.46ng/ml。青春期组明显高于儿童、少年期组。其GH浓度与生长发育及年龄相关 ,分泌量的高峰出现在青春期。本文为临床提供了该年龄段GH水平的参考指标。     

Expression of Growth Hormone by Lymphocytes

In the present study, we evaluated whether mononuclear leukocytes could synthesize and secrete growth hormone (GH) in vitro. Studies using antibody affinity chromatography, high pressure liquid chromatography, and polyacrylamide gel electrophoresis indicate that leukocytes secrete a ～22,000 dalton molecular weight immunoreactive GH (irGH). The irGH appeared to be de novo synthesized since it could be radiolabeled with tritiated amino acids and its production blocked by prior incubation of leukocytes with cycloheximide. The levels of secreted irGH were enhanced by concanavalin A or lipopolysaccharide. By using RNA slot blot analysis, we detected specific GH mRNA present in the cytoplasm of rat leukocytes. Leukocytes from a variety of tissues in rats, including spleen, thymus, bone marrow, and peripheral blood as well as separated spleen T and B cells, were all observed to produce GH RNA and secrete GH from the cells. We conclude that lymphocytes produce a mRNA for irGH and are then able to translate that message and secrete the molecule from the cell. The data suggest a potential regulatory loop between the immune and neuroendocrine systems.     

Plasma Cortisol and Growth Hormone Responses to Intravenous Catheterization

Abstract

Plasma Cortisol and growth hormone (HGH) responses to venous catheterization were studied in 29 volunteer subjects. Repeat catheterizations were performed in 18 individuals. Mean plasma cortisol levels were significantly elevated during the first hour of the initial catheterization experience. Morning and afternoon levels of cortisol were not distinguishable during the first catheterization, but PM levels were significantly lower than AM levels during the second catheterization experience. Growth hormone responses were much more variable than cortisol and were distributed logarithmically. Growth hormone responses tended to parallel cortisol responses during the first catheterization experience. Individuals who listed more symptoms in response to venipuncture and catheterization after finishing their first catheterization had significantly higher cortisol and growth hormone levels during this experience. These data suggest a definite endocrine adaptation to catheterization by the second or third hour of the experience.     

The Autodecomposition of Radiolabeled Human Growth Hormone

Abstract

Human growth hormone (hGH) was radiolabeled with ¹²⁵I, using a gentle lactoperoxidase technique. The stability and decomposition products of this tracer were studied by frequent periodic analysis by Sephadex G-100 chromatography on a long column. Monomeric ¹²⁵I-hGH showed an exponential decline, with a half-life of 61 days. The main radioactive degradation product was iodide, which appeared with a fractional appearance rate of 0.01136 per day. Secondary degradation products were a series of radioactive oligomers of hGH, which appeared with an overall fractional rate of 0.00525 per day. The kinetic data obtained should provide guidelines for the shelf- life and repurification schedule of radioiodinated polypeptides.     

Evidence for a Local Action of Growth Hormone in Embryonic Tooth Development in the Rat

Abstract

Studies in non-dental embryonic tissues have suggested that an interaction between growth hormone and its receptor may play a role in growth and development before the foetal pituitary gland is competent. This study reports the distribution of growth hormone, its rezceptor and binding protein in developing rat tooth germs from embryonic day 17 to 21 and postnatal day 0 using antibodies specific for each of these proteins. Four foetal rats were processed at each time point (E17, EM, E20/21 and postnatal day 0). Following routine fixation and paraffin embedding, sections were treated with antisera to rat growth hormone, rat growth hormone binding protein and growth hormone receptor. Localization of antibody/antigen complexes was subsequently visualized by addition of biotinylated IgG and reaction with streptavidin peroxidase and diaminobenzidine. Assessment of the level of staining was qualitative and based on a subjective rankings ranging from equivocal to very strong staining. Overall, growth hormone and its binding protein were located both in the cellular elements and throughout the extracellular matrix, whereas the growth hormone receptor showed an exclusively intra-cellular location. All three proteins were detectable in cells of the dental epithelium and mesenchyme at the primordial bud stage (E17) which occurs prior to expression of pituitary growth hormone. At the cap stage of odontogenesis (E18-19), numerous cells in both the dental epithelium and mesenchyme were intensely immunoreactive for growth hormone, its binding protein and receptor. In the succeeding early bell stage (E20-21), most of the mesenchymal cells in the dental pulp were mildly positive for these proteins, while the dental epithelium and adjacent mesenchyme were more immunoreactive. At the late bell stage (postnatal day 0), all three proteins were localized in dental epithelium, differentiating mesenchymal cells the cuspal surface facing the epithelial-mesenchymal interface, preodontoblasts, and odontoblasts forming dentine. From these observations, immunoreactive growth hormone, its receptor and binding protein appear to be expressed in odontogenic cells undergoing histodiierentiation, morphodifferentiation and dentinogenesis in a cell-type and stage-specific pattern throughout embryonic tooth development. This suggests the possibility that growth hormone, or a growth hormone-like protein, plays a paracrindautocrine role in tooth development in utero.     

雌二醇对大鼠颌下腺GnRH、GH生成的影响

目的　研究雌二醇 (estradiol- 17β,E2 )对颌下腺促性腺激素释放激素 (gonadotropin releasing hor-mone,Gn RH)和生长激素 (growth factor,GH )生成的影响。方法　采用免疫组织化学的 ABC法。结果　雌二醇促进颌下腺 Gn RH的生成而对 GH的产生有抑制作用。结论　雌二醇可能对颌下腺 Gn RH和 GH的合成起重要的调节作用     

老年原发性高血压患者血清生长激素与胰岛素间的相关性分析

目的 :探讨老年原发性高血压 (EH)患者血清生长激素与胰岛素水平的改变、相关性及其临床意义。方法 :采用放射免疫分析测定了 88例老年原发性高血压患者和 4 0例非高血压患者的血清生长激素和胰岛素水平 ,并进行统计学分析。结果 :EH组血清生长激素水平显著低于对照组 (p <0 0 1 ) ,胰岛素显著高于对照组(p <0 0 1 ) ,两者间呈显著的正相关 (p<0 0 5 ) ,但与平均动脉压均无显著的相关性意义 (p均 >0 0 5 )。Ⅲ期组血清生长激素显著低于Ⅰ、Ⅱ期组 (p<0 0 1 ,p <0 0 5 ) ,Ⅰ、Ⅱ、Ⅲ期组间血清生长激素依次递减 ,方差检验具有显著的差异 (p <0 0 1 ) ,而胰岛素无显著差异 (p >0 0 5 )。 1、2、3级组血清生长激素与胰岛素虽依次递减 ,但无统计学意义 (p >0 0 5 )。低危组、中危组、高危组、很高危组间血清生长激素也依次递减 ,方差检验具有显著的差异 (p <0 0 1 ) ,而胰岛素无显著差异 (p >0 0 5 )。伴心脑血管并发症组血清生长激素水平显著低于无并发症组 (p <0 0 1 ) ,但胰岛素却无显著差异 (p >0 0 5 )。结论 :老年原发性高血压 (EH)患者血清生长激素水平显著低于对照组 ;Ⅲ期组血清生长激素显著低于Ⅰ、Ⅱ期组 ,Ⅰ、Ⅱ、Ⅲ期组间血清生长激素依次显著递减 ;低危组、中危组、高危组、很高     

分娩前后血清生长激素变化的观察

目的 :了解女性血清生长激素 (GH)在妊娠期及分娩前后的变化。方法 :采用放射免疫分析 (RIA)检测 76例正常非孕期妇女、6例妊娠晚期妇女、32例临产期妇女和 2 0例产褥期妇女的血清生长激素 (GH)。结果 :妊娠晚期和临产组血清GH含量明显高于正常组和产褥组 ,差异有显著性 (p <0 0 1 ) ;妊娠晚期组与临产组无明显差异 (p >0 0 5 )产褥组与正常组也无明显差异 (p >0 0 5 )。 结论 :GH在妊娠后期和临产期明显升高 ,反映了母体的正常功能 ,为胎儿的正常发育所必需。分娩后迅速恢复正常 ,表明孕期及妊娠期增高的可能主要是母体中胎血GH的含量     

精神分裂症患者血清催乳素和生长激素水平及与利培酮、氯丙嗪治疗关系的对照研究

目的 :探讨精神分裂症患者的血清催乳素 ( PRL)、生长激素 ( GH)的基础水平与正常人的差异 ,及治疗前后 PRL、GH水平的变化 ,以及利培酮对 PRL、GH的影响。方法 :采用放射免疫法对 2 1例精神分裂症患者治疗前和治疗后第 2、 4、 6周末的 PRL、 GH水平进行测定 ,并与 3 2名正常人为对照 ,同时将药物分为利培酮组 11例和氯丙嗪组 10例。结果 :精神分裂症患者的基础 PRL、 GH水平与对照组无差异 ( P>0 .0 5 ) ,但女性患者 PRL明显低于对照组 ( P<0 .0 5 )。抗精神病药物治疗后 PRL 显著升高 ( P<0 .0 1) ,GH下降 ,但未达显著差异水平。女性患者治疗后 PRL 升高明显 ,为男性的 4 .0 6倍。利培酮治疗 6周末 PRL 为 119.61± 64 .4 2 ng/ml,较治疗前增高显著 ( P<0 .0 1) ,与氯丙嗪组比较无差异 ( P>0 .0 5 )。结论 :支持精神分裂症的多巴胺功能亢进假说 ,抗精神病药物所致 PRL 升高有明显的性别差异 ,利培酮有明显的致 PRL升高作用 ,有较强的拮抗中枢多巴胺作用