胰岛素样生长因子-Ⅰ和胰岛素样生长因子结合蛋白-1与妊高征的关系

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 1(IGFBP—1)与妊高征(PIH)的关系。方法：采用免疫放射法测定50例妊高征孕妇(PIH组)和108例正常孕妇(对照组)的血清 IGF-Ⅰ、IGFBP-1水平，并对其结果进行相关性分析。结果：①妊高征孕妇血清 IGF-Ⅰ水平低于正常孕妇(P<0.05)，且重度妊高征孕妇血清 IGF-Ⅰ水平低于中度和轻度孕妇(P＜0.05，P＜0.01)。②妊高征孕妇血清 IGFBP-1水平高于正常孕妇(P＜0.05)，且重度妊高征孕妇血清 IGFBP-1水平高于中度和轻度孕妇(P＜0.05，P＜0.01)。③两组孕妇血清 IGF-Ⅰ水平与血清 IGFBP-1水平呈负相关(r=-0.386，P＜0.05)。④妊高征孕妇血清 IGF-Ⅰ水平与舒张压呈负相关(r=-0.386，P＜0.05)，血清 IGFBP-1水平与舒张压呈正相关(r=0.632，P＜0.01)。结论：妊高征孕妇血清 IGF-Ⅰ、IGFBP-1水平的高低可反映妊高征的严重程度。     

Decreased serum levels of nutritional biochemical indices in healthy children with marginally delayed physical growth

Biochemical markers of nutritional status (albumin, transthyretin, insulin-like growth factor-I and zinc) were measured in slowly growing two- to five-year-old, low-income Parisian children whose weight-for-height or height-for-age z scores (WHZ or HAZ) were between — 1 and — 2 SD of the NCHS median. The results were compared to controls who were matched for age, sex, and ethnic origin with WHZ and HAZ between — 1 and + 2 SD. Mean serum levels of transthyretin, albumin and insulin-like growth factor-I and mean plasma zinc concentrations were significantly lower in the growth-impaired children than in the controls ( p = 0.002, p = 0.006, p = 0.015, and p = 0.035, respectively). While the height-retarded children had low mean serum insulin-like growth factor-I values, the weight-retarded subjects had decreased levels of albumin, transthyretin and zinc when compared to controls. Lower mean levels of nutritional markers in healthy, slowly growing children suggest that inadequate dietary intakes of zinc, protein and/or energy may result in marginal delays in weight and height gains.     

The prevention or treatment of age-related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF-I or rhTGFβ): a perspective

Boonen S, Broos P, Dequeker J, Bouillon R (Department of Internal Medicine, Division of Geriatric Medicine, the Arthritis and Metabolic Bone Disease Research Unit, the Department of Traumatology and Emergency Surgery and the Laboratory for Experimental Medicine and Endocrinology, Katholieke Universiteit Leuven, Leuven, Belgium). The prevention or treatment of age-related osteoporosis in the elderly by systemic recombinant growth factor therapy (rhIGF-I or rhTGFβ): a perspective (Review). J Intern Med 1997; 242 : 285–90.
Both insulin-like growth factor-I (IGF-I) and transforming growth factor β (TGFβ) have powerful modulatory effects in a variety of tissues. A major target of action is the skeletal system, where they enhance bone formation and decrease matrix degradation, thus playing a part in the maintenance of bone mass. Because of the potent mitogenic effect of these agents on osteoblasts, recombinant IGF-I (rhIGF-I) and recombinant TGFβ (rhTGFβ) have potential as drugs to stimulate bone formation in the prevention and treatment of osteoporosis. Using biochemical markers, subcutaneous rhIGF-I therapy has been shown to increase bone turnover and bone formation in nonosteoporotic older people. However, a corresponding increase in bone mass has not yet been documented nor have there been reports yet on the effects of systemically administered rhTGFβ in humans. Further investigation is required to define the clinical potential of rhIGF-I and rhTGFβ as therapeutic agents in age-related osteoporosis.     

IGF-I与宫内发育迟缓及其结合蛋白的关系

目的：检测宫内发育迟缓（IUGR）儿脐血胰岛素样生长因子-I（IGF-I）、胰岛素样生长因子结合蛋白-3（IGFBP-3）水平,分析这些指标的变化程度与胎儿期生长的关系。方法：将86例脐血标本分为IUGR（即小于胎龄儿）组和适于胎龄儿（AGA）组。采用放射免疫分析（RIA）测定IGF-I水平,免疫放射分析（IR-MA）测定IGFBP-3水平。两组间比较用t检验,两变量之间的关系采用相关回归分析。结果：与AGA组相比,IUGR组脐血IGF-I和IGFBP-3水平显著降低（P均〈0.01）;IGF-I、IGFBP-3均随胎龄及出生体重增加而增加（P均〈0.01）;IGFBP-3与IGF-I呈正相关（P〈0.01）。结论：脐血IGF-I和IGFBP-3的含量可作为判断新生儿生长发育程度的一项客观指标。     

阻塞性黄疸患者生长激素/胰岛素样生长因子-Ⅰ轴变化的研究

目的　探讨阻塞性黄疸患者生长激素/胰岛素样生长因子-Ⅰ轴的变化及其临床意义。方法　对60例男性阻塞性黄疸患者（阻黄组）围手术期血浆生长激素、生长激素结合蛋白、胰岛素样生长因子,内毒素、肝功能及前白蛋白水平进行观察,并与40例男性单纯性胆囊结石患者（对照组）进行比较。结果　生长激素、生长激素结合蛋白、胰岛素样生长因子-Ⅰ在阻黄组分别为7.4μg/L±3.6μg/L、9.1±2.3B/T*100、49.8mg/L±6.6mg/L,较对照组（13.9μg/L±5.7μg/L、13.3±1.6B/T*100、61.4mg/L±6.5mg/L显著降低,差异有显著意义(P<0.01),并与黄疸程度,前白蛋白、内毒素水平相关(P<0.01)。结论　阻塞性黄疸患者生长激素/胰岛素样生长因子-Ⅰ轴存在明显下调。其原因可能与营养障碍、内毒素血症引起的生长激素受体表达受抑有关,并可进一步加重营养障碍和内毒素血症,是介导阻塞性黄疸病理生理改变的重要因素。     

胰岛素样生长因子-Ⅰ及胰岛素样生长因子结合蛋白-3与胎儿宫内发育的关系

目的 检测孕妇静脉血、脐血中胰岛素样生长因子－Ⅰ (IGF－Ⅰ )及胰岛素样生长因子结合蛋白-3(IGFBP-3)水平,探讨 IGF－Ⅰ、 IGFBP-3与胎儿宫内发育的关系。方法 采用美国 DSL公司试剂盒。总计 81例孕妇,其中正常孕妇 38例,妊娠糖尿病孕妇 20例,正常妊娠分娩巨大儿孕妇 23例,采用放射免疫方法测定。 结果 正常组及巨大儿组孕妇静脉血 IGF-I与新生儿体重呈正相关 (r=0.653, r=0.640,两组 P均     

Adult Growth Hormone Deficiency: Current Concepts

The clinical syndrome of adult growth hormone deficiency (AGHD) was widely recognized in the 1980s. In this review, we first describe the clinical features and diagnosis of AGHD and then state the effects of growth hormone (GH) therapy for these patients. The main characteristics of AGHD are abnormal body composition, dyslipidemia, insulin resistance, and an impaired quality of life (QoL) due to decreased psychological well-being. For diagnosing AGHD, the international consensus guidelines have suggested that an insulin tolerance test (ITT) is the gold standard, but in Japan, the growth hormone releasing peptide-2 (GHRP-2) test is available and is recommended as a convenient and safe GH stimulating test. The cut-off for diagnosing severe AGHD is a peak GH concentration of 9 g/L during the GHRP-2 test. Since 2006, GH therapy has been approved for Japanese patients with severe AGHD. For adults, GH replacement therapy should be initiated at a low dose (3 g/kg body weight/day), followed by individualized dose titration while monitoring patients'' clinical status and serum insulin-like growth factor-I (IGF-I) concentrations. A variety of favorable effects of GH replacement have been indicated; however, it has not yet been established fully whether there is a direct effect of GH treatment on reducing mortality.     

Potential applications of GH secretagogs in the evaluation and treatment of the age-related decline in growth hormone secretion

The two classes of GH secretagogs—GH-releasing hormone (GHRH) and the GH-releasing peptides and their analogs (GHRP’s)—retain their ability to endogenous GH secretion in healthy and frail elderly subjects. They have very limited utility in assessment of the state of the GH/IGF-I axis except to confirm an intact pituitary, but they are attractive potential alternatives to GH as therapeutic agents. There is wide interest in the possibility that elevating GH and IGF-I might increase muscle mass, physical strength and performance, and possibly sleep and cognition in aging. The GH secretagogs, like GH, can produce a sustained stimulation of this axis; in contrast to GH, they preserve feedback regulation at the pituitary level and stimulate a near-physiologic pulsatile pattern of GH release. GHRP’s and their nonpeptide analogs are also active when given orally, a significant practical advantage. Short-tern treatment studies have shown that GHRH and the GHRP’s can enhance GH secretion and elevate IGF-I and IGFBP-3 levels; that GHRH may promote sleep; and that these agents are generally well tolerated. Longer-term studies, assessing effects upon body composition and physical and psychological function are underway. Prepared for presentation at “Assessment of the Growth Hormone/IGF-I Axis in Aging,” Bethesda, MD, April 14, 1997.     

Insulin-like growth factor I acts as an angiogenic agent in rabbit cornea and retina: comparative studies with basic fibroblast growth factor

Summary The release of growth factors from ischaemic retina has been hypothesized as the central stimulus for retinal neovascularization in proliferative diabetic retinopathy. Two of the growth factors implicated are insulin-like growth factor-I and basic fibroblast growth factor. We examined the effect of insulin-like growth factor-I on in vivo neovascularization using the established angiogenic model of the rabbit cornea (n=30), and also compared the effects of insulin-like growth factor-I and basic fibroblast growth factor using two new in vivo systems. Either supraphysiologic concentrations of each growth factor (600 g) were injected intravitreally into pigmented rabbits (n=21) or porous polyfluorotetraethylene chambers filled with an emulsion containing collagen and growth factor (500 ng) were placed on the retina surface (n=8). Our results demonstrate that when insulin-like growth factor-I was implanted together with a slow release carrier into the pocket of the normally avascular cornea, insulin-like growth factor-I (10 g/pellet) induced angiogenesis in all rabbits. This degree of angiogenesis was comparable to that previously shown for basic fibroblast growth factor. For the intravitreal studies, the fibrotic component was greater in the basic fibroblast growth factor injected eyes, whereas the vascular component was accentuated in the eyes injected with insulin-like growth factor-I. Light and electron microscopy demonstrated areas of vascular proliferation in both groups. Porous polyfluorotetraethylene chamber studies with insulin-like growth factor-I and basic fibroblast growth factor demonstrated vascular proliferation in the vicinity of the chamber similar to the intravitreal injected eyes, but to a lesser degree than the injected eyes. Our experiments overall support the angiogenic potential of both insulin-like growth factor-I and basic fibroblast growth factor and support distinct but complimentary roles for each growth factor in the pathogenesis of proliferative diabetic retinopathy.     

A quantitative real-time RT-PCR assay for salmon IGF-I mRNA, and its application in the study of GH regulation of IGF-I gene expression in primary culture of salmon hepatocytes

The hormone insulin-like growth factor-I (IGF-I) regulates vertebrate growth. The liver produces most circulating IGF-I, under the control of pituitary growth hormone (GH) and nutritional status. To study the regulation of liver IGF-I production in salmon, we established a primary hepatocyte culture system and developed a TaqMan quantitative real-time RT-PCR assay for salmon IGF-I gene expression. A portion of the coho salmon acidic ribosomal phosphoprotein P0 (ARP) cDNA was sequenced for use as a reference gene. A systematic bias across the 96 well PCR plate was discovered in an initial IGF-I assay, which was corrected when the assay was redesigned. IGF-I mRNA levels measured with the validated assay correlated well with levels measured with an RNase protection assay, and were highest in liver compared with other tissues. We examined the time course of hepatocyte IGF-I gene expression over 48 h in culture, the response to a range of GH concentrations in hepatocytes from fed and fasted fish, and potential effects of variation in IGF-I in the medium. IGF-I gene expression decreased over time in culture in hepatocytes in plain medium, and in cells treated with 5 nM GH with or without a combination of metabolic hormones (1 microM insulin, 100 nM triiodothyronine, and 0.1 nM dexamethasone). GH stimulated IGF-I gene expression at all time points. In cells treated with GH plus metabolic hormones, IGF-I gene expression was intermediate between the controls and GH alone. Increasing concentrations of GH resulted in biphasic IGF-I gene expression response curves in cells from fed and fasted fish, with the threshold for stimulation from 0.5 to 2.5 nM GH, maximal response from 5 to 50 nM, and a reduced response at 500 nM. Medium IGF-I (5 nM) did not affect basal or GH stimulated IGF-I gene expression. This study shows that primary hepatocyte culture and the TaqMan IGF-I assay can be used to study the regulation of hepatic IGF-I gene expression in salmon, and provides the first evidence of a biphasic response to GH concentration in fish hepatocyte culture.