Influence of growth hormone and insulin-like growth factor-I on kidney function and kidney growth

Decreased glomerular filtration rate (GFR) in hypopituitarism and increased GFR in acromegaly suggest that growth hormone (GH) has a substantial effect on renal haemodynamics. Extractive and recombinant human (rh) GH in healthy volunteers increased effective renal plasma flow (ERPF) and GFR by 10% and 15% respectively. Renal response to GH was delayed and occurred at the same time as an increase in plasma insulin-like growth factor (IGF)-I values, whereas infusion of rhIGF-I promptly increased GFR and ERPF, indicating that the haemodynamic response of the kidney to GH is mediated by IGF-I. In chronic renal failure (CRF), the acute effect of GH on GFR is obliterated. This might protect the diseased kidney against the undesired consequences of hyperfiltration. Indeed, rhGH treatment for 1 year in children with CRF did not lead to an accelerated decline in GFR compared with the year before treatment. GH and IGF-I also effect renal growth. Exposure to excessive GH in transgenic mice causes renomegaly and progressive glomerular selerosis. In acromegalic humans, increased renal size and weight and increased glomerular diameter are well known, whereas renal failure is not a long-term hazard. At least in normal and hypophysectomized rats treated with doses comparable with the therapeutic regimens used in stunted children, rhGH increased renal weight but in proportion to the increase in body weight indicating an isometric effect of GH on renal growth. From these data, major renal longterm side effects of rhGH treatment in children with CRF appear unlikely.     

Human growth hormone and growth hormone releasing hormone: A double-masked,placebo-controlled study of their effects on bone metabolism in elderly women

We treated 42 postmenopausal women with decreased bone mass for 12 weeks with human growth hormone, growth hormone releasing hormone, or placebo. Bone density and biochemical markers were determined before and during treatment, and 4 weeks after withdrawal. Biochemical markers of bone formation and resorption increased significantly in the group treated with growth hormone, whereas no changes were seen in the other groups. After withdrawal of therapy the bone markers declined without reaching baseline values. Bone density in the forearm, spine and proximal femur was unchanged in all groups. We conclude that treatment with growth hormone stimulates bone metabolism in elderly postmenopausal women with decreased bone mass.     

Effect of growth hormone on fluoride balance

Fluoride balances were determined in nine children, aged 4 to 18 years, undergoing treatment with human growth hormone. Urinary F was increased in 6 of the 9 subjects during the period of initial treatment. The hyperfluoruria occurred in the face of a preexisting negative F balance. Fecal F did not change, and since the magnitude of the hyperfluoruria could not be correlated with changes in renal function it is likely that it, together with the increases in Ca and hydroxyproline excretion, represents a direct effect of the hormone (or possibly “sulfation factor”) on bone resorption. During the control periods, the F balance data reveal that 10–90% of dietary F (all of which came from food) appeared in the feces; these values are generally higher than those reported for subjects whose intake was primarily from water.     

血清生长激素结合蛋白浓度和肝脏生长激素受体表达与肾病大鼠生长障碍的关系

目的：探讨营养不良、肾病本身和糖皮质激素作为各自独立因素对大鼠血清生长激素结合蛋白（ＧＨＢＰ）及肝脏生长激素受体（ＧＨＲ）表达的影响。阐明ＧＨＢＰ／ＧＨＲ改变与肾病综合征（ＮＳ）大鼠生长障碍的关系。方法２４只周龄相同体重相近的雄性ＳＤ大鼠被随机分成正常,食物对照,阿霉素（５ｍｇ．ｋｇ）肾病的地塞米松（１．８ｍｇ．ｋｇ＾－１．ｄ＾－１）治疗的阿霉素肾病４组。血清ＧＨＢＰ、ＧＨＢＰ－１浓度及肝脏ＧＨＲ     

Growth hormone and insulin-like growth factor-I and mesangial matrix in uremic rats

Combined growth hormone (GH) and insulin-like growth factor-I (IGF-I) therapy has been advocated for clinical use to minimize the diabetogenic effect of GH and enhance their anabolic effects. However, GH has been shown to accelerate the development of glomerular sclerosis in experimental animals and IGF-I mediates the renal effects of GH. The purpose of this study was therefore to examine morphometrically the effects of GH (1 mg intraperitoneally three times a week), IGF-I (50 g/kg body weight subcutaneously twice a day), and combined GH/IGF-I treatments in vivo on mesangial matrix at 3–20 days after 5/6 nephrectomy in 140- to 150-g rats. There were no significant changes in growth and renal function after GH and/or IGF-I treatment. The effects of GH and IGF-I on glomerular size were additive, which were more prominent in juxtamedullary glomeruli. GH induced proportional increases in mesangial area (MA) and glomerular area (GA), whereas IGF-I induced a similar increase in GA without a corresponding change in MA. When compared with GH treatment alone, combined GH/IGF-I treatment resulted in a lesser degree of mesangial expansion despite an enhanced glomerular size. While additional studies are needed to examine the long-term effects of these findings, our results suggest a potentially beneficial effect of combined GH/IGF-I therapy during uremia.     

The effect of growth hormone on the growth failure of chronic renal failure

To investigate the effects of growth hormone (GH) on the reversal of growth failure in uremia, recombinant human GH (rhGH) was administered to rats with chronic renal failure (CRF). The dosage of rhGH was 3 IU/day (i.p.) for 13 days after the induction of CRF by 5/6 nephrectomy. Animals were classified into four groups: untreated nephrectomized rats (NX,n=40), GH-treated nephrectomized rats (NX+GH,n=18), sham-operated rats fed ad libitum (SHAMAL,n=27), and sham-operated rats pair-fed with 10 NX rats (SHAMPF,n=10). NX and NX+GH rats developed a similar and moderate degree of CRF, serum urea nitrogen being (mean±SEM) 49±3 and 54±4 mg/dl, respectively, compared with 16±4 and 19±0 mg/dl in SHAMAL and SHAMPF groups. Weight (56.0±3.3 g) and length (3.5±0.1 cm) gains of NX rats were lower than those of SHAMAL rats (94.2±4.0 g,P<-0.0001 and 4.1±0.2 cm,P<-0.01). Growth of the SHAMPF group and the matched NX rats was not significantly different. Weight (56.2±5.0 g) and length (3.4±0.2 cm) gains of NX+GH and NX rats were similar, the beneficial effect of GH therapy on growth being observed in only those animals with more severe degrees of uremia. This growth-promoting action resulted from greater food efficiency and not from stimulated food intake. The hypercholesterolemia seen in NX rats, 81±2 mg/dl versus 55±3 mg/dl in SHAMAL (P0.0001), was not increased in the NX+GH group, 87±3 mg/dl. There was a positive and significant correlation between serum cholesterol and serum urea nitrogen values in NX and NX+GH animals. This study suggests that growth impairment of mild CRF is mainly due to malnutrition and is refractory to GH administration. GH therapy improves the growth rate of animals with advanced CRF without aggravating their lipid abnormalities.     

Growth hormone binding protein and free growth hormone in chronic renal failure

Chronic renal failure in children is associated with growth failure. While the pathogenesis of uremic growth failure is multifactorial, an abnormal growth hormone/insulin-like growth factor (GH-IGF) axis is an important contributory element. Patients with uremia exhibit insensivivity to the action of GH, as exemplified by high plasma GH levels, low IGF-I activity, and poor somatic growth. This insensitivity can be overcome by supraphysiological doses of exogenous GH. Plasma GH binding protein (GHBP, the circulating ectodomain of the GH receptor) levels are decreased in patients with renal failure, as are hepatic GH receptor levels in animal models. Since GHBP levels are thought to reflect GH receptor levels in tissues, it is likely that the uremic GH insensitivity in humans is mediated by a decreased number of GH receptors. Another implication of the low plasma GHBP is a disproportionate elevation of free plasma GH (the biologically active moiety) relative to total GH, lending additional support to the concept of GH insensitivity in uremia. GH kinetics are altered in renal failure because of: (1) inability to excrete GH and (2) changes in the bound fraction of GH in the circulation.     

生长激素治疗对烧烫伤小儿生长发育的影响

目的：评价短期应用重组人生长激素（rhGH）对小儿烧烫伤的治疗效果及治疗后对其生长发育的影响。方法：选取82例住院烧烫伤患儿,随机分为rhGH治疗组58例和对照组24例。rhGH治疗组在常规治疗的基础上给予rhGH皮下注射0．3IU／kg,每晚1次,连续使用10d。对照组只给予常规治疗,于相应时间皮下注射2m1生理盐水。另选30例发育正常的整形患儿作为正常对照。动态观察应用rhGH（或生理盐水）前1d、应用后5d后,出院时及出院后6、12、18、24个月两组患儿血生长激素、血糖水平;患儿于入院时测量身高、体重,计算体质指数（BMI）,出院后6～24个月进行追踪性观察,与同时期同年龄段北京市正常小儿生长指标进行对比,评价影响。结果：rhGH治疗组创面愈合速度较对照组明显加快;创面愈合后瘢痕增生及痛痒程度明显轻于对照组,差异有显著性（P〈O．05）。rhGH治疗前两组血生长激素水平均明显低于正常水平。rhGH治疗第5天患儿的生长激素水平明显高于正常组水平和对照组（P〈0．001）,至出院时两组均趋于正常。伤后两组血糖水平均有轻度升高,激素治疗第5天恢复正常,但差异无显著性,两组之间各时间比较差异均无显著性。两组出院时体重和BMI均低于北京市儿童正常标准,但两组间身高、体重和BMI差异均无显著性。结论：临床短期小剂量使用生长激素治疗小儿烧烫伤能够加速创面愈合,提高创面愈合质量。创面愈合后小剂量短期应用的生长激素不会对小儿的生长发育造成后续影响。     

生长激素和生长抑素对人结肠癌裸鼠移植瘤模型的影响

目的观察外源性生长激素（GH）和生长抑素（SS）对人结肠癌细胞株HT-29裸鼠移植瘤模型肿瘤生长和裸鼠血清蛋白水平的影响。方法接种结肠癌细胞株HT-29建立裸鼠移植瘤模型。比较移植肿瘤体积、细胞周期分布、增殖指数（PI）、凋亡率、bcl-2和bax mRNA水平．以及裸鼠血清蛋白水平。结果生长抑素能够明显抑制移植瘤的生长（P〈0．05）、降低移植瘤PI（P〈0．05）、促进移植瘤细胞凋亡（P〈0．01）、降低移植瘤bcl-2mRNA表达（P〈0．05）、提高移植瘤baxmRNA表达（P〈0．05），生长激素则表现出相反的作用。生长激素能够改善移植瘤导致的低蛋白血症（P〈0．05）。结论外源性生长抑素能够显著抑制人结肠癌裸鼠移植瘤生长，外源性生长激素单独或联合生长抑素应用能够改善荷人结肠癌移植瘤裸鼠低蛋白血症，但具有潜在的促进肿瘤生长的作用。     

Interactions between growth hormone and dexamethasone in skeletal growth and bone structure of the young mouse

Summary The present study investigated the interactions of growth hormone (GH) and glucocorticoid on skeletal growth and bone structure in young mice. The purpose of this study was to examine the possible prevention by GH of the damage inflicted by dexamethasone (Dex) at sites of skeletal growth and ossification. Dex (1 mg/kg) with or without rat GH (rGH) or bovine GH (bGH), 1 mg/kg, was given for 4 weeks, from age 3–7 weeks, to female ICR mice. Tibiae, humerus, and vertebrae were analyzed morphometrically and biochemically. Growth, as determined by the mouse weight, tibial length, and humerus protein content was found to be compromised by dexamethasone. This was prevented by rGH or bGH. The epiphyseal growth plate width, trabecular bone volume, cortical bone width, mineral bone content, and alkaline and acid phosphatase activity were decreased by dexamethasone. These were prevented by rGH or by bGH. The findings of the present study suggest that in the mouse, GH can decrease or even avoid some of the pathological features in growing bones inflicted by high-dose glucocorticoid treatment.     

生长激素不同应用时间对IVF助孕结局的影响

目的通过分析重组生长激素(rGH)不同应用时间对多周期体外受精(IVF)患者助孕结局的影响,探讨rGH应用于多周期IVF患者的最佳时间。方法选择西北妇女儿童医院生殖中心2017年1月至2018年6月多周期行IVF助孕且采用rGH辅助治疗的198例患者,其中一部分患者采用长期辅助治疗即促排卵前1月开始用rGH直至HCG日,为长期治疗组(109例);另一部分患者采用短期辅助治疗即促排卵同步应用rGH至HCG日,为短期治疗组(89例)。比较两组患者正常受精率、优胚率、临床妊娠率、早期流产率等的差异。结果两组患者间年龄、不孕年限、基础窦卵泡数(AFC)、基础FSH及BMI比较均无显著性差异(P>0.05);促排卵过程中两组患者的Gn用量及Gn天数亦均无显著性差异(P>0.05);长期治疗组和短期治疗组的内膜厚度[(11.80±2.59)mm vs.(10.94±2.40)mm]、获卵数[(10.28±5.59)vs.(8.35±4.88)]、HCG日E2水平[(13 963.90±10 209.89)pmol/L vs.(10 893.43±8 240.21)pmol/L]及HCG...     

不同血液净化方法对尿毒症患者甲状旁腺素水平的影响

目的比较联机血液透析滤过（HDF）和常规血液透析（HD）对尿毒症患者甲状旁腺素（iPTH）水平的影响。方法选择我院血液净化中心2004年6月至2006年12月期间透析龄超过9个月且iPTH明显升高的尿毒症患者60例,其中男38例、女22例,平均年龄43．5岁,平均透析龄（18．6±9．3）月。将患者随机分为HDF组和HD组,每组30例。两组患者每周均透析三次,HDF组为1次HDF、2次HD,每次透析4h。HDF组使用F60滤过器;HD组使用F6HPS透析器,统一低分子肝素抗凝。检测透析前后患者血液血肌酐（SCr）、血尿素氮（BUN）及iPTH水平并计算其清除百分率。结果SCr与BUN清除率在HD组分别为（70.6％±3．2％）和（74．2%±4．0％）,在HDF组分别为（71．8％±2．3％）和（76．2%±3．8％）,两组之间差异无统计学意义。HD组血iPTH值透析前后无显著差异,清除率仅为（1．7%±0．9%）,而HDF组iPTH的清除率为（32．8％±7．8％）,该组透析前后溶质浓度及清除率的差异均有统计学意义。结论两种血液净化治疗方式对小分子物质的清除效果无差异,但HDF对中分子物质（iPTH）的清除效果明显优于HD。定期HDF有利于iPTH的清除、防止iPTH异常导致的钙磷代谢紊乱、降低代谢性骨病等并发症的发生率。     

Renal effects of growth hormone. I. Renal function and kidney growth

Growth hormone (GH) affects renal function and kidney growth. Pituitary-derived or recombinant human GH (rhGH), acting via insulin-like growth factor-1 (IGF-1), increases glomerular filtration rate (GFR) and renal plasma flow (RPF) in GH-deficient as well as in normal adults. Furthermore, GFR and RPF are low in hypopituitarism and elevated in acromegaly. These effects of GH on GFR and RPF have not been demonstrated in moderate renal insufficiency. IGF-1 is implicated in compensatory renal hypertrophy. Markedly elevated levels of serum GH accelerate glomerular sclerosis in rodents, although the significance of these findings for GH treatment in humans is uncertain. rhGH therapy offers great promise to children with short stature from various aetiologies. Preliminary report on the use of rhGH in children with renal disease and after renal transplantation have not shown any consistent change in kidney function, although follow-up times are short. The long-term impact of rhGH therapy on kidney function in short children needs further evaluation.Part II of this review will be published in Pediatr Nephrol (1992) Volume 6, Number 5     

谷氨酰胺和生长激素对短肠综合征患者肠道代偿作用

目的探讨谷氨酰胺和生长激素对短肠综合征(SBS)患者的肠道代偿作用。方法26例短肠综合征患者残余小肠长度为0～100(中位数42.5)cm,手术后接受肠外营养(PN)支持3-52个月,联合应用生长激素(GH)(0.10±0.06)mg·kg-1·d-1和谷氨酰胺(GLN)(0.30±0.17)g·kg-1·d-1进行肠道促代偿治疗。结果26例接受GH加GLN治疗的SBS患者,其中9例(34.6%)治疗后近期内完全摆脱PN;8例(30.8%)经治疗后明显减少了PN用量,从每周需要PN(6.0±1.0)d下降至(4.2±1.0)d,每周PN需要量从(13.6±5.2)L降至(8.2±3.3)L;9例(34.6%)在治疗后仍依赖PN维持。结论经过合适的营养支持和肠道促代偿治疗,大多数短肠综合征患者残留肠道能充分代偿,完全摆脱PN或减少PN用量,长期健康生存。     

Effect of growth hormone on testicular dysfunction induced by methotrexate in rats

Methotrexate (MTX) is a chemotherapeutic agent causing defective oogenesis and spermatogenesis. This study was performed to assess the role of human growth hormone (GH) on testis recovery after treatment with MTX. Forty male Wistar rats were selected and randomly divided into four groups (n = 10): control (vehicle), GH group (0.3 mg kg^?1 GH for 28 days, IP), MTX group (MTX 1 mg kg^?1 week^?1 for 4 weeks, IP) and GH/MTX group (0.3 mg kg^?1 GH for 28 day plus 1 mg kg^?1 week^?1 MTX for 4 weeks, IP). On days 14 and 28, five rats from each group were killed, testes of rats of all groups were removed, spermatozoa were collected from epididymis and then prepared for analysis. MTX caused significant increase in interstitial tissue and capsular thickness and decrease of testicular and body weight (P < 0.05). Moreover, it caused significant decline in seminiferous tubule diameter and epithelium thickness (P < 0.05). There was no obvious change in morphometrical parameters between MTX/GH and control groups. In MTX group, sperm parameters decreased significantly (P < 0.05). Administration of GH plus MTX reduced the effects of MTX on sperm parameters and testosterone concentration. These results suggested that GH had a protective effect on almost all destructive effects caused by MTX in rat testes and thus improved sperm parameters.     

Acidosis prevents growth hormone-induced growth in experimental uremia

The effects of 2 weeks of a daily injection (2 IU/day) of recombinant human growth hormone (GH) were studied in young (60-g) growing rats in two experiments. Experiment 1 was performed in uremic animals (mean plasma creatinine 65–71 mol/l) who were either acidotic (mean bicarbonate 11.5 mmol/l) or had acidosis corrected (mean bicarbonate 26 mmol/l) by addition of sodium bicarbonate to the diet. Experiment 2 used rats with normal renal function (plasma creatinine 25 mol/l) who were either non-acidotic but restricted to the dietary intake of uremic rats or rendered acidotic by ammonium chloride. GH induced an increase in body weight and length in nonacidotic uremic (+33% and +41%) and in non-acidotic food-restricted (+13% and +42%) rats, associated with an increased rate of protein synthesis and little change in plasma insulin-like growth factor 1 (IGF 1). In both acidotic rat groups, GH altered none of the parameters studied. Thus: (1) the presence of severe metabolic acidosis blunts the response to GH in uremic and non-uremic rats and (2) the increment of growth rate does not depend on a rise in plasma IGF 1.     

Alterations of the growth plate in chronic renal failure

Chronic renal failure modifies the morphology and dynamics of the growth plate (GP) of long bones. In young uremic rats, the height of cartilage columns of GP may vary markedly. The reasons for this variation are unknown, although the severity and duration of renal failure and the type of renal osteodystrophy have been shown to influence the height of GP cartilage. Expansion of GP cartilage is associated with that of the hypertrophic stratum. The interference of uremia with the process of chondrocyte differentiation is suggested by some morphological features. However, analysis by immunohistochemistry and/or in situ hybridization of markers of chondrocyte maturation in the GP of uremic rats has yielded conflicting results. Thus, there have been reported normal and reduced mRNA levels for collagen X, parathyroid hormone/parathyroid hormone-related peptide receptor, and matrix metalloproteinase 9, as well as normal mRNA and protein expression for vascular endothelial growth factor and chondromodulin I, peptides related to the control of angiogenesis. In addition, a decreased immunohistochemical signal for growth hormone receptor and low insulin-like growth factor I mRNA in the proliferative zone of uremic GP are supportive of reduced chondrocyte proliferation. Growth hormone treatment improves chondrocyte maturation and activates bone metabolism in the primary spongiosa.This work was presented in part at the IPNA Seventh Symposium on Growth and Development in Children with Chronic Kidney Disease: The Molecular Basis of Skeletal Growth, 1–3 April 2004, Heidelberg, Germany     

重组人生长激素对烧伤大鼠肠粘膜结构及细胞凋亡的影响

目的　探讨重组人生长激素 (rhGH)的早期应用对严重烧伤大鼠小肠粘膜的保护作用。　方法　 30只成年雄性Wistar大鼠随机分为对照组、烧伤组和rhGH组 ,每组 10只。后两组造成2 5 %TBSAⅢ度烧伤创面 ,立即腹腔注射地塞米松 80mg/kg ,从伤后 2h开始分别给予等渗盐水和rhGH(1.33U·kg-1·d-1)。于伤后 30、96h ,观察回肠末端粘膜组织形态、肠上皮细胞超微结构和肠粘膜细胞增殖活性与凋亡率变化。　结果　烧伤组肠粘膜形态结构及上皮细胞损伤严重 ,rhGH组明显减轻 ,基本接近对照组 ;伤后 30h烧伤组和rhGH组肠粘膜细胞增殖指数 (proliferativeindex ,PI)均明显高于对照组 (P <0 .0 5～ 0 .0 1) ,但两组之间差异无显著性意义 ;伤后 96h ,rhGH组PI较烧伤组和对照组均明显升高 (P <0 .0 1)。烧伤组肠粘膜细胞凋亡率较对照组明显升高 (P <0 .0 1) ,rhGH组凋亡率较烧伤组 (P <0 .0 1)和对照组 (P <0 .0 5 )明显下降。　结论　rhGH能促进严重烧伤后肠粘膜细胞增殖 ,但作用缓慢 ;能抑制肠粘膜细胞凋亡 ,而且作用迅速、效果明显 ,并可能通过抑制作用减轻肠粘膜损伤 ,维护形态结构的基本正常。     

生长激素促进烫伤鼠肝、创面组织胰岛素样生长因子-Ⅰ及其结合蛋白-3 mRNA的表达

目的　研究重组生长激素 (rhGH)在促进创面愈合过程中对烫伤大鼠肝、创面组织胰岛素样生长因子 Ⅰ (IGF Ⅰ ) /胰岛素样生长因子结合蛋白 3(IGFBP 3)mRNA表达的影响。方法制作大鼠深Ⅱ度烫伤模型 ,每日早上 9点皮下注射rhGH 0 .3IU/d ,疗程 1 0d。逆转录 聚合酶链反应 (RT PCR)检测肝、创面组织IGF Ⅰ /IGFBP 3mRNA表达 ;酶联免疫吸附试验 (ELISA)检测血IGF Ⅰ /IGFBP 3浓度 ;免疫组织化学检测Ⅰ、Ⅲ型胶原的表达。结果　用rhGH治疗 1 0d ,烫伤大鼠肝、创面组织IGF Ⅰ /IGFBP 3mRNA的表达、血IGF Ⅰ的水平较对照组明显升高 (P <0 .0 1 ) ;Ⅰ、Ⅲ型胶原的含量较对照组明显增多 (P <0 .0 1 ) ;而创面愈合时间平均提前 3d。结论　rhGH可通过增加肝、创面组织IGF Ⅰ /IGFBP 3mRNA的表达 ,促进创面愈合。