Measurement of biological activity of somatotropin in hypophysectomized rats

目的：建立测定生长激素（ＧＨ）在体生物活性的方法．方法：以去垂体大鼠体重增长（ＢＷＧ）和胫骨骺软骨板宽度（ＴＥＷ）为指标，观察动物性别、给药途径、次数和周期不同对效应的影响；同时进行４ｄＢＷＧ，６ｄＢＷＧ和６ｄＴＥＷ法，测定ＧＨ的效价（平行线３×３设计）．结果：♀和♂ｓｃ和ｉｍ给药以及每日给药１次和２次的ＢＷＧ和ＴＥＷ差异无显著意义．给药６ｄ比给药４ｄ引起较大的ＢＷＧ和ＴＥＷ（Ｐ＜００５）．４ｄＢＷＧ法和６ｄＢＷＧ法在００２０－０５００ＩＵ·ｄ－１有较好的λ值（００６６０和０１７４７）和ｒ值（０９０００和０９２３７）；４ｄＢＷＧ，６ｄＢＷＧ和６ｄＴＥＷ法测得ｒｈＧＨ的效价为４６１３２，３９８２９和４８０２３ＩＵ／ａｍｐ．６ｄＢＷＧ法有较小的λ值和较低的ＡＲＦＬ值．结论：可在同一组去垂体大鼠体内同时用４ｄＢＷＧ，６ｄＢＷＧ和６ｄＴＥＷ法测ＧＨ活性，以６ｄＢＷＧ法较好．     

生长激素对糖尿病及其微血管病变的影响

目的 :探讨生长激素对糖尿病及其微血管病变的影响。方法 :采用放射免疫法测定 6 7例Ⅱ型糖尿病患者及 18例正常人的血清生长激素 (GH)及胰岛素 (INS)水平。结果 :糖尿病合并微血管病变组 ,空腹生长激素 (FGH)明显高于正常对照组 (P <0 .0 1)及糖尿病无微血管病变组 (P <0 .0 1)。糖尿病无微血管病变组的FGH与正常对照组的FGH相比未见明显差异 (P >0 .0 5 )。餐后 2h的生长激素 (PGH)在 3组之间均无显著差异 (P >0 .0 5 )。FGH与HbA1c、空腹血糖 (FBS)呈正相关 (r=0 .5 46 ,P <0 .0 1;r=0 .437,P <0 .0 1) ,与UAER呈正相关 (r=0 .486 ,P <0 .0 1) ;FGH与病程无相关 (r=0 .2 2 ,P >0 .0 5 ) ,与FINS无相关 (r =- 0 .0 2 9,P >0 .0 5 )。结论 :GH水平的增高 ,与糖代谢紊乱有关 ,参与了糖尿病微血管病变的发生。     

采用定点基因缺失突变技术在大肠杆菌中分泌鲑鱼生长激素

目的：为获得与天然鲑鱼生长激素一致的基因工程产物,对已构建的鲑鱼生长激素基因分泌型表达质粒ｐＯｓＧＨ１５３进行改造,删除所编码表达产物氨基端多余的９个碱基,方法：采用ＰＡＬＴＥＲ系统进行寡聚核苷酸指导下的基因定点缺失突变。突变质粒ｐＯｓＧＨ１５８经限制性酶切图谱及Ｓｏｕｔｈｅｒｎ印迹杂交分析加以证,结果：含有表达质粒ｐＯｓＧＨ１５８的大肠杆菌株经ＩＰＴＧ诱导后提取周质帽白,经ＳＤＳ－ＰＡＧＥ及免疫     

国产生长激素治疗生长激素缺乏症的疗效观察

了解国产人生长激素（ｈＧＨ）的治疗效果。方法：对１５例未经生长激素治疗的生长激素缺乏症（ＧＨＤ）病人（均经精氨酸和可乐宁两项生长激素激发试验明确诊断,生长激素峰值均小于 １０ μｇ／Ｌ）应用国产分泌型基因重组人生长激素（ｒｈＧＨ）进行治疗,剂量为０．１ｕ／（ｋｇ·ｄ）睡前脐周皮下注射,治疗时间６个月。结果：１５例ＧＨＤ病人６个月身高平均增长（６．３４±０．９４）ｃｍ,生长速度由治疗前的（３．３３±０．４９）ｃｍ／年增加到治疗后的（１２．６８±１．８６）ｃｍ／年。结论：国产人生长激素治疗效果达到国外同类产品水平,而价格仅为进口产品的１／６左右。可安全有效地用于治疗ＧＨＤ身材矮小病人。     

Growth Hormone (GH) Secretion in Primary Adrenal Insufficiency: Effects of Cortisol Withdrawal and Patterned Replacement on GH Pulsatility and Circadian Rhythmicity

We studied the effects of cortisol withdrawal and patterned replacement upon spontaneous GH secretion and circadian rhythmicity in 7 patients with Addison's disease. Hydrocortisone was administered in physiological daily total dosages, and all resulting plasma cortisol values were 2–15 g/dl. It was given in 3 pulsatile modes: simulating physiological rhythm, reverse diurnal rhythmicity and continuous pulsatility. All modes of cortisol administration increased mean 24h, GH pulse amplitude and interpulse GH levels. During saline infusions circadian GH rhythmicity was preserved, with GH being at its highest between 2400–0400 h. Administration of hydrocortisone in any mode did not modify circadian GH rhythmicity. We conclude: Cortisol replacement in physiological daily doses increases GH output in patients with Addison's disease by augmenting GH pulse amplitude and interpulse levels. This is likely due to the attenuation of hypothalamic somatostatin (SRIF) secretion by physiologic levels of cortisol. By inference, it implies that cortisol deficiency leads to diminution of GH output with low GH pulse amplitude, likely as a result of an augmented hypothalamic somatostatin secretion. However, circadian rhythmicity of GH secretion is glucocorticoid-independent.     

The effect of growth hormone on the development of diabetic kidney disease in rats.

BACKGROUND: Nephropathy is the most severe complication of diabetes mellitus. We investigated the effect of exogenous growth hormone (GH) administration on renal function and matrix deposition in the streptozotocin (STZ) model of type I-diabetic rat. METHODS: Adult female STZ-diabetic rats (D), non-diabetic control rats injected with saline (C) and control and diabetic rats injected with bovine GH for 3 months (CGH and DGH, respectively) were used. RESULTS: The usual renal hypertrophy seen in D animals was more pronounced in the DGH group. Creatinine clearance increased only in the D rats, but not in the other groups, including DGH. Albuminuria was observed in the D animals but was significantly elevated in the DGH group. Glomeruli from DGH animals showed more extensive matrix accumulation (manifested as an increase in mesangial/glomerular area ratio). Renal extractable insulin-like growth factor (IGF-I) mRNA was decreased in the D and DGH groups, but renal IGF-I protein was not significantly increased. Renal IGF binding protein-1 was increased in the D groups and further increased in the DGH group, at both the mRNA and protein levels. CONCLUSIONS: GH-treated diabetic rats had less hyperfiltration and more albuminuria, concomitant with more glomerular matrix deposition, when compared with regular diabetic animals. This was associated with a significant increase in renal IGFBP-1, and dissociated from IGF-I changes. Thus, in this model, GH exacerbates the course of diabetic kidney disease.     

生长激素受体及其生物学效应的研究进展

恶性肿瘤呈高代谢状态,仅通过输注热量和蛋白质并不能有效地减轻机体的分解状态.而生长激素在综合治疗中,能改善病人的营养不良和负氮平衡,提高疗效和耐受性.其作用的关键就是与生长激素受体(GHR)结合.现就GHR的表达和功能以及受体后信号对目的基因的调节、自我调节作一综述.     

GROWTH HORMONE RESPONSE TO FEEDING IN TERM AND PRETERM NEONATES

ABSTRACT. Plasma growth hormone concentrations were measured in 248 healthy term and preterm infants. At birth growth hormone concentrations in cord blood from both term and preterm babies were approximately 100-fold higher than those in blood drawn from healthy adults. By the sixth postnatal day basal pre-feed levels had fallen in term neonates by 65% and a marked postprandial rise was apparent; preterm infants did not show this initial fall in preprandial hormone levels nor was any response to feeding seen. However a fall in preprandial concentrations accompanied by the development of postprandial surges in growth hormone occurred during the next 2 weeks so that by 24 days the postprandial rise was similar to that of term neonates on the sixth day. We conclude that although the initial postnatal changes in plasma growth hormone concentrations are different in preterm and term infants, feeding is a major stimulus to growth hormone secretion in both groups of neonates. Further work is needed to define the precise role of this hormone in neonatal metabolic adaptation.     

HUMAN SOMATOTROPIN

Three analogs of the carboxyl terminal plasmin fragment of human somatotropin, [Nle¹⁷⁰, Ala^165,182,189]-human somatotropin-(145–191), [Nle¹⁷⁰, Ala^165,182,189]-human somatotropin-(140–191), and [Lys^135,136,138, Glu^137,139, Nle¹⁷⁰, Ala^165,182,189]-human somatotropin-(135–191) have been synthesized by the solid-phase method. The synthetic peptides were assayed for growth-promoting activity and their potency was found to be comparable to that of [S-carbamideomethylcysteine^165,182,189]-human somatotropin-(141–191) which was derived from the native hormone.     

The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency

AIMS: To investigate the absorption profile and estimate the bioavailability of three doses of recombinant human growth hormone (rhGH) smaller than 2 IU in females with GH deficiency (GHD). A second aim of the study was to compare the mean 24 h GH concentrations after s.c. injection of rhGH with the physiological mean 24 h GH concentration of healthy females of comparable age, height, and BMI. METHODS: Fourteen female patients with substituted GHD, and 14 healthy females of comparable age, height, and BMI were studied. All GHD patients underwent 24 h GH sampling after s.c. injection of rhGH in doses of 0.6, 1.2, or 1.8 IU. In addition, these patients underwent a 4 h GH sampling after i.v. injection of rhGH (1 IU). In healthy subjects, blood was withdrawn every 10 min for 24 h to determine the physiological GH profile. RESULTS: A s.c. dose of 0.6 IU resulted in a mean and maximum GH concentration of 0.95+/-0.04 mU l(-1) and 2.62+/-0.09 mU l(-1). A doubling (or tripling) of the rhGH dose resulted in a doubling (or tripling) of the mean and maximum GH concentration. The time of maximum GH concentration was reached on average after 261+/-27 min. Mean GH concentration in healthy females was comparable with the mean GH concentration after a s.c. dose of 1.2 IU. Mean availability of the s.c. injected dose was 63%+/-4%. CONCLUSIONS: A dose of 1.2 IU resulted in a mean GH concentration comparable with the mean physiological GH concentration in healthy females of comparable age, height, and BMI.