细胞因子调节垂体MtT/S细胞中人生长激素基因启动子的活性

目的:探讨细胞因子白介素-11(IL-11)、睫状神经营养因子(CNTF)和转化生长因子(TGF-β)对大鼠垂体MtT/S细胞中人生长激素(hGH)基因启动子活性的影响及其与垂体特异性转录因子Pit-1蛋白的关系。方法:采用荧光素酶报告基因的方法。首先建立含hGH基因启动子(-484～30 bp)和荧光素酶融合基因的稳定转化MtT/S细胞系,然后用细胞因子刺激,检测细胞培养液和细胞裂解液中GH的含量,反映它们对GH分泌和合成的影响;检测MtT/S细胞内荧光素酶的变化,说明细胞因子对hGH基因启动子活性的作用。将Pit-1蛋白表达质粒(pcDNA-pit-1-cDNA)单独转染或与Pit-1反义寡核苷酸(Pit-1OND)共转染于稳定转化的MtT/S细胞中,观察加入细胞因子后荧光素酶的变化,探讨细胞因子的作用与Pit-1蛋白的关系。结果:IL-11(20 nmol/L)、CNTF(10 nmol/L)能刺激大鼠垂体MtT/S细胞中GH的分泌和合成,增强MtT/S细胞中荧光素酶的表达,分别增加到对照组的134%、122%。TGF-β(5 nmol/L)能减少GH的分泌和合成,抑制荧光素酶的表达到对照组的72%。Pit-1蛋白过表达和表达被抑制对细胞因子的调节作用没有影响。结论:IL-11、CNTF和TGF-β通过调节大鼠垂体MtT/S细胞中hGH基因启动子活性影响GH的合成,Pit-1蛋白可能不参与这一调节作用。     

激素对T淋巴细胞生长激素基因表达调控的影响

目的 :探讨各种激素对T淋巴细胞GH基因表达的影响。方法 :构建含人GH调控序列的荧光素酶报告基因质粒PGL2 GH luc,然后转染入T淋巴细胞系———JurkatE6 1细胞中 ,在培养液中分别加入各种激素。结果 :各浓度的GH、GHRH对Jurkat细胞中荧光素酶的表达有抑制作用 (P <0 0 1) ,而高剂量的TRH( 10、10 0nmol/L)和SS( 10 0nmol/L)对Jurkat细胞中荧光素酶的表达也有抑制作用 ( P<0 0 5 )。结论 :T淋巴细胞中GH基因的表达受下丘脑激素和GH的调节。     

激素对T淋巴细胞生长激素基因表达调控的影响1

目的探讨各种激素对T淋巴细胞GH基因表达的影响.方法构建含人GH调控序列的荧光素酶报告基因质粒PGL2-GH-luc,然后转染入T淋巴细胞系--JurkatE6-1细胞中,在培养液中分别加入各种激素.结果各浓度的GH、GHRH对Jurkat细胞中荧光素酶的表达有抑制作用(P＜0.01),而高剂量的TRH(10、100nmol/L)和SS(100nmol/L)对Jurkat细胞中荧光素酶的表达也有抑制作用(P＜0.05).结论T淋巴细胞中GH基因的表达受下丘脑激素和GH的调节.     

细胞因子对T细胞生长激素基因表达的影响

目的 探讨各种细胞因子对T细胞生长激素（GH）基因表达的影响。方法 构建含人GH调控序列的荧光素酶报告基因质粒pGL2-GH-luc，然后转染入T淋巴细胞系Jurkat E6-1细胞中，在培养液中分别加入各种细胞因子。结果 生理浓度的IL－1β，TNF－β和IFN－γ，对Jurkat细胞中荧光素酶的表达具有抑制作用（P＜0．05）。结论 细胞因子参与了调节淋巴细胞GH基因的表达。     

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。     

生长激素基因

生长激素基因与人绒毛膜生长催乳素基因密切相关，由５个同源性程度很高的基因共同组成基因簇，位于人第１７号染色体长臂的ｑ２２－２４带上，其中只有生长激素结构基因（ＧＨ－Ｎ）能在垂体中表达，表达产物９０％为有活性的２２ｋＤａ ｈＧＨ，１０％为２０ｋＤａ ｈＧＨ。ＧＨ－Ｎ基因的启动子是５＇端上游的前２８９ｂｐ，它含有ＧＨＦ－１因子。反式作用因子、甲状腺素和糖皮质激素的结合位点，它们控制着ＧＨ－Ｎ基因表达的     

人生长激素启动子调控TNF-α表达载体的构建及体外靶向基因治疗垂体生长激素腺瘤

 目的 构建人生长激素启动子（hGHp）调控的基因治疗载体pSNAV2.0-hGHp-TNFα并探索其对体外垂体生长激素腺瘤的抑制作用。方法 以pSNAV2.0-hGHp-EGFP和pSNAV2.0-TNFα为基础通过酶切、连接反应构建pSNAV2.0-hGHp-TNFα,用脂质体转染法验证hGHp的靶向转录活性,用ELISA检测治疗基因TNFα的表达并用MTT法检测体外TNFα基因表达对垂体生长激素腺瘤的抑制作用。结果 所得质粒pSNAV2.0-hGHp-TNFα的测序结果正确;pSNAV2.0-hGHp-EGFP 只在GH3细胞检测到绿色荧光而在对照细胞中未检测到绿色荧光;转染了pSNAV2.0-hGHp-TNFα的实验组中GH3细胞的生长较对照组明显受抑制（P<0.05）。结论 首次成功构建了质粒pSNAV2.0-hGHp-TNFα,且其可以明显抑制体外垂体生长激素腺瘤的生长。     

生长激素释放激素和胰高血糖素对成人及生长激素缺乏患者生长激素分泌的影响

本文报告正常成人和成年生长激素缺乏(GHD)患者血清生长激素(GH)对GH释放激素(GHRH)和胰高血糖素(G1u)的反应。肌注G1u后血糖失升高后降低,血糖下降是兴奋GH分泌的因素。联合注射G1u/GHRH后的血清GH峰值部GH反应曲线下面积等于单独注射G1u和GHRH的和。二例对GHRH有GH分泌反应的GHD患者,对单独注射G1u无GH分泌反应。他们的GH分泌对联合注射G1u/GHRH与单独注射GHRH的反应相同。作者认为注射G1u引起的血糖下降可能是通过抑制下丘脑释放生长抑素从而引起GH的分泌。     

胰岛素样生长因子Ⅰ放射免疫分析及其临床初步应用

建立血清胰岛素样生长因子Ⅰ（IGF－Ⅰ）的放射免疫分析（RIA）方法并初步将其应用于临床。采用血标本通过酸性乙醇提取冷冻再沉淀法,提取率达91．5％±4．4％;用乳过氧化酶法以碘－125标记IGF－I,RIA反应液中含提取液（或标准液）50μL,抗体200μL（最终滴度1：10000）,(125)I－IGF－Ⅰ200μL（约13000cpm）,4℃反应过夜,双抗分离。RIA回收率为98．1％～105．0％,批内变异系数5．4％～7．5％,批间变异系数9．1％～10．7％,灵敏度达0．01nmol／L。用此法测得垂体性诛儒患者血清IGF－Ⅰ的浓度为5．4±1．7nmol／L,它明显低于同龄正常组（49.3±26．6nmol／L）的IGF－I浓度（P＜0．001）;测得肢端肥大症患者血清IGF－Ⅰ的浓度为107．7±25．6nmol／L,它明显高于同龄正常组（26．3±12．2nmol／L）的IGF－Ⅰ浓度（P＜0．001）。RIA测定血清IGF－Ⅰ,灵敏度高,准确可靠,对垂体性侏儒及肢端肥大症的诊断有重要参考价值。     

生长激素对大鼠阿霉素性心肌病心肌细胞凋亡的影响

目的探讨生长激素（Growth hormone，GH）对大鼠阿霉素（Adriamycin，ADR）心肌病心肌细胞凋亡及其相关基因蛋白BCL-2、BAX表达的影响。方法30只雄性Wistar大鼠，体重200—250g，随机分为3组：对照组、ADR组和GH＋ADR组。用原位末端标记法（TUNEL）标记凋亡的心肌细胞，用免疫组织化学方法检测BAX和BCL-2的蛋白表达。结果与对照组比较，ADR组心肌细胞凋亡指数明显升高（P〈0．05），GH＋ADR组细胞凋亡指数低于ADR组（P〈0．05）。ADR组BAX蛋白表达明显高于对照组（P〈0．05），BCL-2蛋白表达明显低于对照组（P〈0．05）。GH＋ADR组BAX的蛋白表达明显低于ADR组（P〈0．05），但高于对照组（P〈0．05）；BCL-2的蛋白表达明显高于ADR组（P〈0．05），接近对照组。结论心肌细胞凋亡是导致阿霉素心肌病的主要原因，GH干预治疗可减少阿霉素心肌病的心肌细胞凋亡，这可能与GH能提高BCL-2/BAX比值有关。     

Lowering Cortisol enhances growth hormone response to growth hormone releasing hormone in healthy subjects

Cortisol is known to influence growth hormone release probably by modulating somatostatin tone. We examined the effect of metyrapone (the 1 β-hydroxylase inhibitor) treatment on growth hormone response to growth hormone releasing hormone (1 μg kg^-1 body wt). Six healthy male subjects were tested on two occasions 1 wk apart. On one occasion they received metyrapone followed by growth hormone releasing hormone and on the other placebo followed by growth hormone releasing hormone. In all subjects metyrapone produced a significant drop in Cortisol levels. Together with this drop there was a significant enhancement of growth hormone response to growth hormone releasing hormone. The GH response was negatively correlated with the Cortisol level. Growth hormone release in response to growth hormone releasing hormone challenge is thus seen to be heavily influenced by Cortisol levels.     

The panacea of growth hormone

Growth hormone is one of the latest tools against AIDS. Serono's Serostim (somatropin) is the only growth hormone to receive Food and Drug Administration (FDA) approval to treat wasting. HIV-positive individuals show a dramatic suppression of growth hormone, and people with AIDS have practically none. The decrease in growth hormone is also associated with decreasing T-cell counts. The mechanisms in growth hormone production and their role in metabolism and nutrition are described. Serostim is very expensive, and the Serono SeroCare program has limited the cost to $36,000 per year. The program is managed by the National Organization for Rare Diseases. The method of creating growth hormone from the recombinant DNA proteins (rDNA) family is described.     

Pathology of growth hormone excess

This paper briefly reviews the pathology of growth hormone excess. Prolonged oversecretion of growth hormone is associated with elevated serum growth hormone as well as somatomedian C levels and the clinical signs and symptoms of acromegaly or gigantism. Morphologic studies, including immunohistochemistry and electron microscopy, revealed that several distinct morphologic lesions can be present in the pituitary gland of patients with acromegaly or gigantism. Although substantial progress has been achieved during the last two decades, more work is required to correlate the morphologic features of adenoma cells with their biologic behavior. We feel that the future can be viewed with optimism and further exciting results can be expected by the interaction of pathologists, clinical endocrinologists and basic scientists.     

16例伴生长激素缺乏的多种垂体激素缺乏患者的临床特点及生长激素治疗效果分析

目的探讨伴生长激素缺乏(GHD)的多种垂体激素缺乏症(MPHD)患者的临床特点以及生长激素(GH)治疗效果。方法回顾性分析16例伴有生长激素缺乏的多种垂体激素缺乏患者的临床资料。结果本研究纳入了16例MPHD的患者,其中伴甲状腺功能减退症9例、伴低促性腺激素性性腺功能低减13例和伴肾上腺皮质功能减退6例。臀位、足先露和难产等不良生产史患者10例。骨龄(11.0±3.5)岁,明显落后实际年龄。L-Dopa-GH激发试验GH峰值为(0.14±0.17)ng/m L,GH治疗平均剂量(0.11±0.02)IU/kg。治疗后IGF-1水平及生长速度均明显增加。结论排除下丘脑、垂体占位等病变后,伴GH缺乏的MPHD患者在纠正其他轴系激素缺乏后,使用GH治疗可明显改善身高,并且无严重不良事件发生。     

Effects of growth hormone releasing hormone on rat ovarian steroidogenesis

During the last decade, it has been shown that each part ofthe somatotrophic axis can influence granulosa cell function.Growth hormone releasing hormone (GHRH) may be effective throughthe release of hypophyseal growth hormone (GH) and the subsequentincrease of insulin-like growth factors (IGF). There is alsosome evidence that GHRH could act directly on ovarian function.The aim of this study was to determine the mechanism throughwhich GHRH affects granulosa cell steroidogenesis in the ovary.Granulosa cells were obtained from immature, oestrogen-treatedrats supplemented with or without follicle stimulating hormone(FSH) in vivo and were cultured for 48 h to evaluate steroidproduction. GHRH was administered either in vivo at the sametime as FSH, or in vitro in the presence or absence of testosteroneand FSH. Our results show that co-treatment with GHRH and FSHin vivo induced significant increases in plasma IGF-I concentrationsand steroid production by cultured granulosa cells. The additionof GHRH to culture medium did not significantly alter steroidproduction by either non-differentiated (no FSH in vivo) ordifferentiated (FSH in vivo) granulosa cells. In contrast, treatmentin vitro with IGF-I significantly increased steroidogenesisha both cases. Our results suggest that any physiologicallysignificant effect of GHRH on ovarian function is probably tobe exerted via activation of the somatotrophic axis and thesubsequent amplification of ovarian FSH responsiveness by IGF-I.     

Growth hormone deficiency and growth hormone therapy in Ullrich-Turner-Syndrome

Summary In a girl with Ullrich-Turner-Syndrome (gonadal dysgenesis 45, XO) and growth hormone deficiency, 10 U of human growth hormone/m² body surface area/week increased the growth rate from 2.0 to 4.1 cm/year. Doses of up to 36 U/m²/week did not improve the growth rate in 4 girls with Ullrich-Turner-Syndrome who had normal plasma growth hormone concentration and incretion. We conclude that growth hormone therapy is unsuccessful in dwarfism in Ullrich-Turner-Syndrome and should be reserved for patients with proven growth hormone deficiency.Supported by Deutsche Forschungsgemeinschaft, SFB 51/C10     

Normal growth hormone secretion is rare after microsurgical normalization of growth hormone levels in acromegaly

The effect of microsurgery on growth hormone (GH) secretion was studied in 34 patients with acromegaly. All patients showed enlarged sella volumes according to encephalography and macroadenomas at surgery. Preoperative GH levels were elevated in all 34 patients and 14 had concomitant hyperprolactinemia. There was a correlation between basal GH levels and sella size. Visual field defects, suprasellar extension, long duration of the disease, hyperprolactinemia and aneuploidy were noted in patients with low as well as high levels of GH preoperatively. The average reduction of GH levels in the total series was 71 +/- 21% (mean +/- SD). A notably similar reduction of GH levels was seen regardless of preoperative GH levels, concomitant hyperprolactinemia, visual field defects, size of the adenoma, invasive growth or increasing experience of the surgeon. Therefore, normal GH levels after surgery were reached mainly in patients with moderate GH increments preoperatively. GH levels were normalized by surgery in 15 patients but only four of these showed normal GH response to TRH and iota-dopa tests. Thus, only four patients (12%) fulfilled these criteria for cure of GH homeostasis.     

Episodic patterns of growth hormone secretion and growth hormone status of normal and tibial dyschondroplastic chickens

Growth hormone status of normal and tibial dyschondroplastic (TD) birds was determined in 25 d old male chicks genetically selected for high and low incidence of TD. Birds were surgically prepared with indwelling venous catheters and blood samples remotely removed at 20 min intervals for 6 h to establish secretory patterns. Birds were maintained under a 16L:8D cycle, with free access to feed and water at all times. In a second experiment, secretory capacity was evaluated by administering a 10 micrograms/kg body weight dose of thyrotrophin releasing hormone (TRH). Blood samples were removed at 0, 5, 10, 20, 30, 60 and 120 min post-infusion of either TRH or saline (control). All birds displayed pulsatile patterns of GH secretion, with an average peak duration of 60 min and a 90 min inter-peak interval. Dyschondroplastic birds exhibited 50% higher mean peak amplitudes than normal birds (P less than .06), however, this difference was not translated into overall mean or total (curve area) differences. The magnitude of response to a TRH challenge was greater (P less than .10) for TD than for normal birds. In view of the relationships observed in other species between secretory pattern characteristics such as peak amplitude, and growth characteristics, it is suggested that differences in GH status of dyschondroplastic relative to normal birds may be related to initiation of the TD lesion.