Specificity of the effect of growth hormone on the DNA content in lymphocyte nuclei of hypophysectomized rats

The effect of growth hormone on the DNA content in lymphocyte nuclei in the thymus, spleen, and lymph nodes was investigated cytophotometrically. In hypophysectomized rats growth hormone was shown to increase the DNA content in nuclei of medium lymphocytes of these organs but did not change its content in small lymphocytes. Lymphocytes of the thymus were most sensitive to the action of growth hormone. The DNA content in the nuclei of these cells increased as early as 1 h after injection of the hormone and reached its maximum after 4 h. Other hormones with anabolic action (insulin, thyroxine, testosterone) caused no increase in DNA in the thymocyte nuclei during this period. It is concluded that growth hormone has high affinity for cells of the lymphoid organs and, in particular, for thymocytes (medium lymphocytes of the thymus).Laboratory of Biological Standardization of Hormones, Institute of Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR N. A. Yudaev.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 9, pp. 1126–1128, September, 1976.     

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.     

Subcellular shift of the hepatic growth hormone receptor with progression of hepatitis C virus-related chronic liver disease

AIMS: To evaluate the cytoplasmic and nuclear expression of hepatic growth hormone receptor (GHR) in different stages (S0, S1, S3 and S4, according to Knodell's classification) of chronic liver disease (CLD) and in hepatocellular carcinoma (HCC). METHODS AND RESULTS: Liver specimens from 31 patients with hepatitis C virus-related CLD, five patients with HCC and nine controls were examined for expression of hepatic GHR by immunohistochemistry with MAb 263. Cytoplasmic and nuclear staining were evaluated as a percentage of positively stained cells. The cytoplasmic expression of GHR was comparable between normal liver and S0 hepatitis, while it progressively decreased in S1, S3 and S4 CLD (P < 0.01). Conversely, nuclear GHR showed increased expression in S3 and S4 CLD (P < 0.05). No differences were observed between HCC and normal liver in terms of GHR immunoreactivity. CONCLUSIONS: This is the first study to show that the subcellular expression of hepatic GHR changes with the progression of CLD. The increase in nuclear expression of GHR with advanced stages of CLD suggests that GH may act directly at the nuclear level to promote hepatocyte proliferation/regeneration.     

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。     

Human growth hormone treatment in prepubertal children with achondroplasia

We studied the effects of recombinant human growth hormone (GH) treatment in 6 prepubertal children with achondroplasia. The patients' age ranged from 2 11/12 to 8 5/12 years and the GH dose was of 0.1 IU/kg/day subcutaneously. Auxological assessments and bone age determinations were performed 6 months before, at the beginning, and after 6 and 12 months of therapy. The growth velocity increase during the whole year of treatment ranged from 1.1 to 2.6 cm/year in 3 patients while in the others no variation was detected. No side effects were observed during the trial apart from a slight advancement of bone age in two patients. MRI at the cervicomedullary junction and CT scan of the base of the skull did not show any variation of the dimensions of the foramen magnum at the end of the trial compared to baseline. Our study shows that r-hGH can safely increase short-term growth velocity in some but not all prepubertal children with achondroplasia. Our data confirm the individual variability in the response to the GH treatment. © 1996 Wiley-Liss, Inc.     

重组人生长激素对内毒素血症大鼠的治疗作用

目的 :观察重组人生长激素 (rhGH)对大鼠内毒素血症的治疗效果。方法 :76只SD大鼠随机分为正常对照组、内毒素血症组 (仅腹腔注射鸵鸟株大肠杆菌 (1 5ml/kg ,1× 1 0 10 cfu/L)及治疗组 (腹腔注射鸵鸟株大肠杆菌后行rhGH肌肉注射 (2 2 5IU/kg/d)。内毒素血症组及治疗组又依观察时点再分为 1天、3天两个亚组。采用放射免疫分析方法测定血浆肿瘤坏死因子 α(TNF α)浓度并观测大鼠血压的变化。结果 :与正常对照组相比 ,无论是内毒素血症组还是治疗组 ,1天时其大鼠血浆TNF α浓度均明显升高 (P <0 .0 5 ) ;虽然两组大鼠血压都降低 (P <0 .0 5 ) ,但治疗组大鼠血压降低幅度明显小于内毒素血症组 (P <0 .0 0 1 )。 3天时 ,内毒素血症组大鼠血浆TNF α浓度降至正常对照水平 ,而治疗组大鼠血浆TNF α浓度却明显低于正常对照组 (P <0 .0 0 1 )及内毒素血症组 3天水平 (P <0 .0 5 )。结论 :rhGH能明显减轻内毒素血症大鼠血压的下降 ,对内毒素血症大鼠具有较理想的治疗效果 ;rhGH减轻血压下降的机制可能与其能抑制TNF的释放等有关     

One-year recombinant growth hormone therapy does not improve hemoglobin state and morphology of erythrocytes in growth hormone deficient children

An increase in growth rates of children suffering from growth hormone deficiency (GHD) subjected to recombinant growth hormone treatment (rGHT) was shown to be accompanied by acceleration of metabolic processes that may stimulate oxygen consumption in various organs and tissues. Therefore, oxygen-transporting properties of RBC should undergo considerable changes during the rGHT. The aim of this study was to examine the effects of rGHT on erythrocyte shape and hemoglobin state in GHD children. The level of oxyhemoglobin (Oxy-Hb) in RBC was analyzed by Raman spectroscopy. The RBC count, mean corpuscular hemoglobin (MCH), mean corpuscular volume (MCV) and other parameters were calculated. The blood of eleven treatment-naive prepubertal children with GHD (aged 3–9, median 5.7 years) was examined and compared with control group (aged 5–7; median 6.0 years) at three time points: 0, 3 and 12 months of rGHT. Before rGHT, the MI in GHD children was higher (median 0.48 vs 0.14 p = 0.0018) and the RBC count was lower (median 4.20 vs 4.96 10¹² cells/L p = 0.0022) than in control group. After the treatment, cell count in GHD patients did not differ significantly from the control group, but Oxy-Hb level became higher (median 0.64 vs 0.41 p = 0.0075). During rGHT, MCV decreased (median 80.3 vs 83.2 μm³ p = 0.0231). Morphological and functional characteristics of erythrocytes in GHD children were shown to differ significantly from the healthy control group. A twelve-month rGHT partially improved some of the studied parameters but Oxy-Hb level and echinocyte count remained high.     

黄体生成素及其受体在大鼠肝脏的定位

目的观察黄体生成素(LH)及其受体(LHR)在大鼠肝脏的定位分布,为研究LH是否参与肝代谢功能的调节提供形态学依据。方法应用免疫荧光组织化学双标染色技术,在激光共聚焦扫描显微镜下观察染色结果。结果大鼠肝细胞既呈LH阳性又有LHR阳性,LH和LHR免疫反应阳性物质均分布在大鼠肝细胞的细胞质,细胞核为阴性。不同部位的肝细胞LH及其受体免疫反应强度存在差别。结论 LH及其受体存在于大鼠肝脏细胞,可能对肝脏的功能起调节作用。     

乳糖化人生长激素放射免疫分析方法的研究

目的：探讨鼠肝、肾匀浆中乳糖化生长激素（ｈＧＨ－Ｌ）和人生长激素（ｈＧＨ）的放射免疫分析（ＲＩＡ）方法。方法：取正常小鼠肝或肾匀浆，再在匀浆液中准确加入不同量的ｈＧＨ－Ｌ和ｈＧＨ，制得不同浓度的工作液，参照常规ＲＩＡ方法制作标准曲线。再取静脉注射ｈＧＨ－Ｌ或ｈＧＨ后不同时刻的小鼠肝和肾，经匀浆处理后，应用制作的标准曲线测定肝和肾的ｈＧＨ－Ｌ或ｈＧＨ浓度，以评价ｈＧＨ－Ｌ的体内动力学行为，并为该分析     

GH与EGFR受体后信号交联在GH促进青春期大鼠生长板软骨细胞增殖中的作用

目的: 观察促性腺激素释放激素类似物(GnRHa)处理后青春期大鼠生长板体外培养的软骨细胞内是否存在生长激素(GH)与表皮生长因子受体(EGFR)之间的信号交联(cross-talk)。方法: 3周龄雌性SD大鼠开始注射GnRHa至7周龄;随后分离培养5-8只大鼠胫骨生长板软骨细胞,在GH作用前分别加入JAK2阻断剂AG490(1 nmol/L、10 nmol/L和100 nmol/L)、EGFR酪氨酸激酶阻断剂AG1478(0.1 nmol/L、1 nmol/L和10 nmol/L)和表皮生长因子(EGF)中和抗体(0.1 mg/L、1 mg/L和10 mg/L);采用四氮甲基唑蓝(MTT)以及免疫组化法测定增殖细胞核抗原(PCNA),观察不同阻断剂对软骨细胞增殖的影响;采用Western blotting检测软骨细胞p-ERK1/2及p-EGFR的表达。结果: GH作用后具有浓度依赖性地促进软骨细胞增殖和增加p-ERK1/2及p-EGFR水平的作用,100 μg/L时作用最为明显。AG490及AG1478几乎能完全抑制GH促进软骨细胞增殖和激活ERK1/2及EGFR的作用。 而EGF中和抗体仅能部分抑制GH的作用。结论: GH通过激活JAK2而激活其下游的ERK通路,实现其直接促细胞增殖效应。GH亦能通过激活EGFR及其信号转导通路促进细胞增殖效应,表明GH通路和EGF通路间存在相互作用。     

Familial isolated growth hormone deficiency

A family is reported with isolated growth hormone deficiency in two children, their mother and, presumably, also in two maternal uncles and their maternal grandmother. Autosomal dominant inheritance is the best explanation. Isolated growth hormone deficiency is apparently a heterogeneous condition, including autosomal dominant, autosomal recessive as well as non-genetic diseases.     

生长激素对慢性肾衰患者的免疫调节作用

生长激素(GH)是一种亲水性球蛋白,主要分泌于腺垂体.同时免疫器官,如胸腺、脾脏和外周血细胞,也可分泌GH,而GH受体在各种淋巴细胞中也有表达.GH除能够促进机体生长、代谢外,还具有一定的免疫调节作用.慢性肾衰患者存在着明显的免疫抑制,细胞免疫及体液免疫均受损,在长期血透患者中表现明显,如高感染性疾病并发率,注射疫苗后的反应性较差,恶性肿瘤发生率较正常人偏高.同时慢性肾衰患者也存在着生长激素抵抗现象,血液循环中生长激素水平正常甚至偏高,但生物活性偏低.慢性肾衰儿童生长较正常儿童迟缓,成人蛋白质分解代谢增强,合成代谢不足,而外源性生长激素在慢性.肾衰中的应用可起到一定的免疫调节作用.     

丝胶对Ⅱ型糖尿病大鼠海马生长激素/胰岛素样生长因子-1轴的作用

目的:探讨丝胶对Ⅱ型糖尿病大鼠海马生长激素(GH)/胰岛素样生长因子-1(IGF-1)轴的作用.方法:雄性SD大鼠随机分为正常对照组、糖尿病模型组、丝胶治疗组和阳性对照组.2％链脲佐菌素3d连续腹腔注射的方法建立Ⅱ型糖尿病大鼠模型后,丝胶治疗组和阳性对照组大鼠分别给予丝胶和二甲双胍灌胃治疗35 d.ELISA法检测各组大鼠血清GH和IGF-1水平,免疫印迹和RT-PCR法分别检测大鼠海马GH、生长激素受体(GHR)和IGF-1蛋白和mRNA的表达.结果:与正常对照组大鼠比较,糖尿病模型大鼠血清GH水平、海马GH的表达明显升高,血清IGF-1水平、海马GHR和IGF-1的表达明显降低;与糖尿病模型组大鼠比较,丝胶治疗组大鼠血清GH水平、海马GH的表达明显降低,血清IGF-1水平、海马GHR和IGF-1的表达明显升高.结论:丝胶可通过调节糖尿病海马GH/IGF-1轴的异常变化减轻海马损伤.     

Growth and growth hormone therapy in children with achondroplasia: A two-year experience

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8–12.2 years of age) and 12 girls (5.7–2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week. Auxological assessments were performed 6 months before, at initiation of, and at 6, 12, and 24 months following initiation of growth hormone (GH) therapy. Before initiating GH therapy, hypothalamic-pituitary and thyroid functions were evaluated. Levels of serum insulin-like growth factor (IGF)-I and IGF binding protein (BP)-3 (IGFBP-3) were assessed, as was GH response to provocative stimuli. GH responses in two stimulation tests were normal for all but three children. During the first semester of GH treatment, a significant increase in height velocity (HV), from 3.2 to 8.3 cm/year, was observed in all children. However, during the second semester, a relative decrease in growth rate was observed. By the end of the first year, HV had increased from 3.2 to 6.9 cm/year (mean, 3.7 cm/year; range, 1.1–8 cm/year) in 13 children and remained unchanged in two children. HV declined progressively during the next 12 months and, by the end of the second year of treatment, had increased in seven of the nine children who had completed 2 years of therapy (mean increase, 3.1 cm/year); two children did not respond to GH therapy, as shown by the lack of increase in HV. Sitting-height (SH) to standing-height ratio % (SH%) remained unchanged throughout GH therapy, and no significant change in skeletal maturation was observed. In conclusion, hGH treatment resulted in an increased growth rate in some children with achondroplasia; however, this increase waned during the second year of treatment. Children with the lowest pretreatment HVs seemed to benefit most from GH therapy. Nonetheless, the usefulness of GH treatment in achondroplasia will be known only when a study of final height is completed. Am. J. Med. Genet. 72:71–76, 1997. © 1997 Wiley-Liss, Inc.     

Correlation between exon 3 polymorphism of growth hormone receptor gene and the responses to rhGH therapy

Objective: To investigate the correlation between the exon 3 polymorphism of growth hormone receptor (GHR) gene and the responses to the recombinant human growth hormone (rhGH) therapy in children with short stature. Methods: Forty-five growth hormone deficiency (GHD) children (male: 30, female: 15, aged 10.39±2.73 yrs) and twenty-five idiopathic short stature (ISS) children (male: 15, female: 10, aged 10.58±2.56 yrs) admitted to our hospital were included. The polymorphism of exon 3 of GHR gene was determined using multiple PCR amplification. Treatment duration for each subject was at least 12 months. On this basis, we evaluated the correlation between treatment efficiency of rhGH therapy and GHR exon 3 polymorphism, GHD, and treatment duration. Results: Significant difference was noted in the growth velocity (GV) of GHD children with a genotype of GHRfl compared with those with a genotype of GHRd3 (9.44±2.35 vs. 11.36±2.49, P < 0.05). Meanwhile, the GV of ISS patients with a genotype of GHRfl were remarkably decreased compared with those with a genotype of GHRd3 (8.74±2.36 vs. 11.18±2.44, P < 0.05). For the children with peak GH response of less than 5 ng/ml, statistical difference was noted in the GV of children with a genotype of GHRfl compared with those with a genotype of GHRd3 (9.55±2.76 vs. 10.84±1.53, P < 0.05). For the patients with peak GH response to clonidine or pyridostigmine bromide of > 5 ng/ml, a satisfactory response to rhGH therapy was noted in children with a genotype of GHRd3 compared with those of GHRfl (P < 0.05). Conclusions: GHRd3 was correlated with the response to rhGH therapy in children with short stature. For the patients with the same genotype, GHD caused no obvious effects on the final height. However, for the patients with peak GH response of > 5 ng/ml, a satisfactory response to rhGH therapy was noted in children with a genotype of GHRd3 compared with those of GHRfl (P < 0.05). A higher treatment efficiency was obtained in those received rhGH at an early age.     

Growth and growth hormone in Turner syndrome: Looking back,looking ahead

Short stature is the most ubiquitous feature of Turner syndrome (TS). Today, many girls with TS are treated with recombinant human growth hormone (GH) to accelerate growth in childhood and to improve adult height. Here, we will review the history of our understanding of growth in TS, reflect on the path of clinical trials ultimately leading to regulatory approval for clinical use of GH, discuss factors associated with growth outcomes and survey the current unanswered questions about growth and GH in TS.