表皮生长因子与地塞米松对早产大鼠肺发育的影响

目的 探讨表皮生长因子(EGF)和地塞米松(DEX)对早产大鼠呼吸窘迫综合征的防治作用.方法 将72只胎鼠随机分为EGF、DEX 2个干预组和9 g/L盐水对照组,于孕19 d剖腹取胎鼠,称取胎鼠体质量;通过光镜、图像分析观察胎鼠肺的形态结构;用免疫组织化学方法检测胎鼠肺组织表面活性蛋白A和B(SP-A及SP-B)的表达,并通过计算免疫组织化学平均灰度值比较各组SP-A及SP-B的表达.结果 EGF组胎鼠体质量与对照组比较无明显差异[(1.398 60±0.073 05)g,(1.386 30±0.037 27)g],DEX组胎鼠体质量明显低于对照组[(1.319 20±0.053 26)g,(1.386 30±0.037 27)g].光镜下EGF组与DEX组胎肺可见到明显的肺泡腔结构,对照组肺泡腔尚未发育;图像分析表明EGF组与DEX组胎肺的肺泡腔与肺泡间隔面积之比均大于对照组(Pa<0.01).SP-A及SP-B在3组中均有表达,与对照组比较,SP-A及SP-B在EGF组和DEX组中的表达强度均显著增强(Pa<0.01).结论 EGF和DEX在SD大鼠妊娠第16-18天作用于母体,均能促进胎鼠肺的形态发育和表面活性物质的合成,对早产大鼠呼吸窘迫综合征的发生具有防治作用.二种药物对胎鼠肺的影响程度无明显不同,但产前应用DEX会降低胎鼠体质量,EGF无此不良反应.     

胰岛素样生长因子与新生大鼠高氧肺损伤的关系

近年来的研究表明，胰岛素样生长因子(insulin-like growth factor，IGF)在肺损伤中扮演了重要角色。为进一步探讨其与新生儿高氧肺损伤的关系，2002年10月～2003年6月，我们对新生大鼠高氧肺损伤模型中IGFs的表达及维甲酸(Retinoic acid，RA)干预结果进行了对比观察，现报道如下。     

宫内发育迟缓与胰岛素样生长因子及其结合蛋白关系研究

为了解脐血中胰岛素样生长因子_I(IGF -I)、胰岛素样生长因子结合蛋白_3(IGFBP_3)的水平变化与胎儿期生长的关系 ,将86例新生儿脐血标本分为宫内发育迟缓 (IUGR ,即小于胎龄儿 )组 (22例 )及适于胎龄儿 (AGA)组 (64例 )两组 ,采用竞争性放射免疫分析法 (RIA)测定IGF_1水平、非竞争性免疫放射分析法 (IRMA)测定IGF BP_3水平。结果显示 ,与AGA组相比 ,IUGR组脐血中IGF_1和IGFBP_3水平显著降低 (P均<0.01) ;IGF_1、IGFBP_3水平均随胎龄及出生体重增加而增加 (P均<0.01) ;IGFBP_3与IGF_1呈正相关 (P<0.01)。提示IUGR与IGF_1及其结合蛋白降低密切相关 ;脐血中IGF_1、IGFBP_3水平与胎龄及出生体重呈正相关     

宫内发育迟缓与胰岛素样生长因子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-1(IGF-1)、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。采用竞争性放射免疫分析法(RIA)测定IGF-1水平,非竞争性免疫放射分析法测定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-1和IGFBP-3水平显著降低(P均<0.01);IGF-1、IGFBP-3均随胎龄及出生体重增加而增加(P均<0.01);IGFBP-3与IGF-1呈正相关(P<0.01)。结论 脐血IGF-1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生化指标。     

胰岛素样生长因子与生长发育的研究进展

胰岛素样生长因子(IGFs)及其受体、结合蛋白、结合蛋白酶构成IGF轴，在儿童生长发育中起重要作用。IGFs通过自分泌和旁分泌机制对肌母细胞、成骨细胞、脂肪细胞、神经细胞、造血细胞等的增殖分化起调节作用；IGFs还能促进蛋白质的合成、葡萄糖氧化与脂肪分解；同时促进免疫细胞的分化与成熟，保护肠道黏膜屏障，提示重组IGFs可用于疾病的治疗。     

IUGR大鼠胰岛素样生长因子与小肠及体格发育关系的研究

目的：生后早期的生长主要受营养的调控,营养物质-胰岛素-胰岛素样生长因子(IGF)轴在胎儿宫内发育迟缓(IUGR)生长追赶及胃肠发育中起着重要的作用,而胃肠发育又与营养物质的吸收、生长追赶关系密切。目前国内有关IUGR出生时小肠发育状况报道甚少,且仅限于IUGR出生时胃肠形态结构的观察。该研究探讨生后早期不同蛋白质和热卡水平的营养干预如何调控IGF系统及影响IUGR大鼠的小肠发育和体格生长追赶,并追踪至成年期。方法：采用孕母饥饿法建立IUGR模型。64只IUGR新生鼠随机分为4组：IUGR正常饮食组(SC组),饮食中蛋白含量20%;IUGR高蛋白组(SH组),饮食中蛋白含量占30%;IUGR低蛋白组(SL组),饮食中蛋白含量为10%;IUGR高热卡组(SA组),饮食中热卡较其它组高20%。16只正常新生鼠为正常对照组(C组)予以正常饮食。幼鼠3周断乳后继续予原饮食模式1周,第4周起各组均予正常饮食喂养。分别于出生时及生后第4周、12周测定各组大鼠的血清IGF-1、胰岛素生长因子结合蛋白-3(IGFBP-3)浓度及体重、身长和小肠重量、长度。结果：IUGR大鼠虽然宫内营养不良,但SH组及SA组呈快速小肠发育和体格生长追赶伴IGFs水平明显升高,其中4周时SH组IGFs水平显著高于其余各组(P0.05)。SL组4周和8周的体重、身长、小肠长度和重量均低于其它4组(P0.05)。结论：4周时血清IGF-1是反映生长追赶的灵敏指标,与小肠和体格的生长追赶呈正相关,至成年期这种相关性消失。     

胰岛素样生长因子结合蛋白2在新生鼠肺发育中的作用

目的探索胰岛素样生长因子结合蛋白(IGFBP)2在新生鼠肺发育中的作用。方法SD孕鼠80只分为4组,即A:对照组;B:地塞米松(Dex)1组;C:Dex2组;D:维A酸(RA)组。A、B、D组分别于孕18～20d皮下注射生理盐水、Dex,腹腔注射RA;C组于生后1～3d皮下注射Dex。各组分别于孕18、20、21d(C组孕期不取)、生后1、3、5、7、10、14、21d取肺标本作形态学检查、免疫组织化学、Westernblot及RT PCR检测。结果1.肺组织形态学:B、C组早期肺泡发育提前,数目多,壁薄,晚期则明显落后于A、D组。2.IGFBP2肺表达:A组中IGFBP2主要在胎肺组织中表达,孕18d左右表达最强,随后表达渐减弱。B、C组表达趋势同A组,但生后各时间点均较A组增强;D组生后各时间点均较A组减弱。3.Westernblot:IGFBP2多肽表达强度各组孕18d表达最强,随后渐降低;B、C组生后各时间点表达强度明显高于A组(P均<0.01);D组各时间点浓度均明显低于A组(P均<0.01)。4.RT PCR:IGFBP2mRNA表达的强度变化规律与其肽浓度变化相似。结论IGFBP2在肺发育过程起重要作用,其浓度过高则影响肺发育。     

胰岛素样生长因子与生长发育的研究进展

胰岛素样生长因子 (IGFs)及其受体、结合蛋白、结合蛋白酶构成IGF轴 ,在儿童生长发育中起重要作用。IGFs通过自分泌和旁分泌机制对肌母细胞、成骨细胞、脂肪细胞、神经细胞、造血细胞等的增殖分化起调节作用 ;IGFs还能促进蛋白质的合成、葡萄糖氧化与脂肪分解 ;同时促进免疫细胞的分化与成熟 ,保护肠道黏膜屏障 ,提示重组IGFs可用于疾病的治疗     

6个月内婴儿血清生长激素、胰岛素样生长因子-1、胰岛素样生长因子结合蛋白-3变化与体格发育的关系

目的 探讨6个月内婴儿血清生长激素(GH)、胰岛素样生长因子-1(IGF-1)、胰岛素样生长因子结合蛋白-3(IGFBP-3)水平变化与体格发育值的关系.方法 对85例低出生体质量儿(LBWI)及29例足月适于胎龄儿于生后3 d、3个月、6个月时进行放射免疫法检测血清GH、IGF-1、IGFBP-3,同时测量婴儿体质量、身长、头围、胸围.结果 生后3 d小于胎龄儿的体格发育值和血清GH、IGF-1、IGFBP-3均分别低于适于胎龄儿(P均＜0.05),早产儿均小于足月适于胎龄儿(P＜0.05).3、6个月时LBWI的体格发育值和血清GH、IGF-1、IGFBP-3浓度均低于足月适于胎龄儿(P＜0.05).生后3 d、3个月、6个月时各体格发育值与各激素浓度均呈正相关.结论 新生儿血清GH、IGF-1、IGFBP-3浓度水平与胎儿生长发育有密切关系.LBWI生后6个月血清GH、IGF-1、IGFBP-3仍存在相对低水平状态,体格发育值仍落后于正常足月儿.     

胰岛素样生长因子与胎儿生长发育

胰岛素样生长因子(IGFs)在胎儿生长发育中的作用已日益引起人们的重视。本文就IGFs家族的概况及它们在胎儿脑、肺、肾上腺、骨发育中的作用及与胎儿宫内生长迟缓的关系予以综述     

胰岛素样生长因子1及胰岛素样生长因子结合蛋白3与胎儿宫内生长发育的关系

目的　通过测定新生儿脐血中胰岛素样生长因子 1(IGF 1)和胰岛素样生长因子结合蛋白 3(IGF BP 3)水平 ,研究其与出生体质量、身长及胎盘质量等生长参数间的关系 ,探讨影响胎儿宫内生长发育的内分泌因素。方法　将新生儿根据出生体质量与胎龄的关系分为适于胎龄儿 (AGA)组与小于胎龄儿 (SGA)组 ,分别测定两组出生时身长、体质量和胎盘质量 ,同时取新生儿脐血用免疫放射法测定IGF 1和IGFBP 3含量。结果　1) 10 5例新生儿中 79例AGA和 2 6例SGA ,其出生时身长、体质量和胎盘质量 3个参数比较均存在显著差异(P <0 .0 0 1) ,AGA组显著高于SGA组 (P <0 .0 0 1) ;2 )两组脐血IGF 1和IGFBP 3比较 ,AGA组IGF 1和IGF BP 3水平均高于SGA组 (P <0 .0 1和P <0 .0 0 1) ;3)出生时身长、体质量和胎盘重质 3个生长参数均与IGF 1和IGFBP 3呈显著正相关 (P均 <0 .0 0 1)。结论　 1.出生时身长、体质量和胎盘质量可用来评价AGA和SGA的生长发育。 2 .AGA脐血中IGF 1和IGFBP 3明显高于SGA。 3.胎儿自身分泌IGF 1和IGFBP 3与上述生长参数密切相关 ,其对胎儿的生长发育起重要调节作用。IGF 1和IGFBP 3可作为胎儿宫内生长发育的指标     

Relationship of insulin-like growth factor-I, insulin-like growth factor binding protein-3, insulin, growth hormone in cord blood and maternal factors with birth height and birthweight

BACKGROUND: To determine whether the following factors are related to birthweight or birth height, we measured insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein (IGFBP)-3, insulin and growth hormone (GH) levels in cord blood and also observed the relationship between birthweight, birth height and maternal factors. METHODS: One hundred and ninety-four cord bloods were collected, 106 from males and 88 from females. Three newborns were small for gestational age (SGA), 168 were appropriate (AGA) and 23 were large (LGA); 21 newborns were preterm and 172 were term. RESULTS: Levels of IGF-I and IGFBP-3, measured by enzyme-linked immunosorbent assay, were significantly lower in preterm babies (35.3 +/- 15.1 and 1025.6 +/- 562.8 ng/mL, respectively) than in term babies (61.6 +/- 39.5 and 1252.6 +/- 403.2 ng/mL, respectively; P < 0.01), but neither insulin nor GH levels, measured by radioimmunoassay, showed any significant difference between the two groups (P > 0.05). Among term babies, IGF-I and IGFBP-3 levels were significantly higher in the LGA group (96.1 +/- 34.1 and 1544.7 +/- 418.1 ng/mL, respectively) than in the AGA group (56.4 +/- 37.6 and 1212.8 +/- 383.4 ng/mL, respectively; P < 0.01). Levels of IGF-I and IGFBP-3 showed significant correlation with birthweight and length, respectively (P < 0.01), although GH and insulin levels did not (P > 0.05). There was a significant correlation between IGF-I and IGFBP-3 levels (P < 0.01, r = 0.64), but IGF-I and IGFBP-3 levels showed no relationship with GH or insulin levels. Birthweight correlated significantly with prepartum maternal weight, maternal weight gain and maternal height (P < 0.05), but birth length correlated significantly only with maternal height (P < 0.05). CONCLUSIONS: Our results suggest that fetal growth depends on fetal levels of IGF-I and IGFBP-3 and maternal factors, not on insulin or GH. Levels of IGF-I and IGFBP-3 may not be regulated by insulin alone, but by the complex interactions between several factors, such as insulin, GH and maternal factors.     

早期营养干预对宫内生长迟缓大鼠胰岛素样生长因子和小肠发育及生长追赶的影响

目的　探讨早期营养干预对宫内生长迟缓 (IUGR)幼鼠血清胰岛素样生长因子 (IGF)和小肠发育及生长追赶的影响。方法　将 2 4只IUGR新生雌鼠和 8只正常新生雌鼠随机分为 4组 :IUGR模型组 ,IUGR低蛋白组 ,IUGR高蛋白组 ,正常对照组。于生后 4周时检测各组大鼠血清IGF1、胰岛素样生长因子结合蛋白 3(IGFBP3)浓度、体重、身长和小肠重量、长度及肠黏膜组织结构变化。结果　 4周时IUGR高蛋白组血IGF1、IGFBP3和小肠黏膜绒毛高度、吸收表面积均显著高于对照组和IUGR模型组 (P <0 .0 5或P <0 .0 1) ;小肠重量、长度和体重、身长与对照组比较无显著性差异 (P均 >0 .0 5 )。结论　生后头 4周予高蛋白饮食早期营养干预IUGR幼鼠 ,可通过促进小肠发育达到满意的体格生长追赶。血清IGF1是反映生长追赶的灵敏指标     

Growth hormone insensitivity syndromes: a preliminary report on changes in insulin-like growth factors and their binding proteins during treatment with recombinant insulin-like growth factor I

Serum levels of insulin-like growth factor (IGF) binding proteins (IGFBPs) 1, 2 and 3 were studied by radioimmunoassay in 29 patients with growth hormone (GH) insensitivity syndromes (GHIS) before and during treatment with IGF-I. As in normal subjects, there was a highly significant correlation between IGFs and IGFBP-3 but not between IGFs and the other binding proteins, though IGFBP-3 represented only about one-third of the total IGFBP concentration. In 6 patients with GH deficiency and in 5 patients with GHIS, the pharmacokinetic profile of IGF-I after a single injection was strongly dependent on the IGFBP-3 concentration. A slight but significant increase in IGFBP-3 was observed coincident with the IGF-I peak, whereas IGFBP-2 increased after a delay of about 10 hours. In the patients with GHIS, chronic IGF-I treatment, with twice-daily injections for 6 months, caused a significant steady decline of IGF-II and an increase in IGFBP-2, but had no effect on IGFBP-1 and IGFBP-3 levels. During IGF-I treatment, an inverse relationship between baseline IGF-I and GH levels was observed. The data suggest that total IGF-I and IGF-IL serum levels are determined mainly by IGFBP-3, even in extreme situations such as GHIS, while other IGFBPs are less important. The IGFBP-3 concentration seems to be a major regulator of the pharmacokinetics of exogenous IGF-I, which, in turn, influences IGFBP-3 levels. This effect of IGF-I on IGFBP-3 is not through induction of IGFBP-3 synthesis, but possibly by reduction of IGFBP-3 clearance. Finally, IGF-I administration suppresses GH secretion.     

维甲酸对高氧暴露下新生大鼠肺组织中Ⅰ型胶原含量的影响

为探讨维甲酸对高氧暴露下新生大鼠肺组织中Ⅰ型胶原含量的影响。将生后2d的SD大鼠随机分为4组：（1）空气 生理盐水组；（2）高氧 生理盐水组；（3）高氧 地塞米松组；（4）高氧 维甲酸组。（2），（3）和（4）组持续暴露于85%O2中，于生后14d采用免疫组化和原位杂交方法对肺组织中Ⅰ型胶原蛋白，转化生长因子βⅠ，Ⅱ型受体，肺组织中Ⅰ型胶原mRNA行定位，半定量检测，作HE染色行辐射状肺泡计数，结果显示，与高氧 生理盐水组相比，高氧 维甲酸组辐射状肺泡计数显著增加，肺组织中Ⅰ型胶原蛋白表达明显增强，而Ⅰ型胶原基因表达和转化生长因子βⅠ，Ⅱ型受体表达显著减弱，阳性表达明显改变的分布主要在支气管上皮细胞，肺泡上皮细胞和肺内间质细胞，提示维甲酸通过对Ⅰ型胶原mRAN转录后调控和调节Ⅰ型腾的蛋白的降解而啬 肺内胶原含量，从而起到逆转高氧对肺发育抑制作用。     

Effects of insulin-like growth factor I treatment on the molecular distribution of insulin-like growth factors among different binding proteins

The molecular distribution of insulin-like growth factor I (IGF-I) and IGF-II among the IGF binding proteins (IGFBPs) was studied before and during IGF-I therapy in Ecuadorean adults with growth hormone receptor deficiency (GHRD). Of the total circulating IGF-I and IGF-II, 70% was carried by the 150 kDa complex in normal subjects, while in patients with GHRD, 50% of serum IGF-I, but only 30–35% of serum IGF-II, was measured within the 150 kDa IGFBP-3 region. Administration of IGF-I altered the concentration of IGF-I and IGF-II, although the percentage of total IGF measured within each IGFBP region was not affected, as the increase in IGF-I and the decrease in IGF-II were proportional. Similarly, serum concentrations of IGFBP-3 and the acid-labile subunit, measured by radioimmunoassay, were unaltered. Thus, administration of IGF-I to patients with GHRD was unable to correct the aberrant distribution of IGFs among the IGFBPs.     

Effect of retinoic acid on renal development in newborn mice treated with an angiogenesis inhibitor

Background: A mouse model of impaired renal development was developed and the effect of retinoic acid (RA) was investigated in this animal model. Methods: An angiogenesis inhibitor (SU1498) was injected s.c. into day 3 C57BL/6 newborn mice to create a model of arrested renal development. RA (2 mg/kg) was injected i.p. for 10 days. Morphometry and immunohistochemistry were done. Results: Mice injected with SU1498 demonstrated deranged renal development in tubular structure and glomerular tuft area. Cortical thickness and area of glomerular tuft were significantly decreased after vascular endothelial growth factor (VEGF) inhibitor, and were significantly restored by RA. The length of capillary loops/glomerulus, the number of podocytes/glomerulus, and density of peritubular capillaries on CD31 immunostaining were significantly decreased by VEGF blocking and recovered by RA. Conclusions: VEGF plays a major role in renal development, and RA reverses the inhibited development caused by an angiogenesis inhibitor.     

生长发育迟缓与胰岛素样生长因子的关系

目的提高由于生长激素－胰岛素样生长因子（ＧＨ－ＩＧＦ）轴异常引起的生长发育迟缓诊断的准确性。方法分别收集门诊６８例生长发育迟缓儿童运动激发试验前后２次血清和１４例住院患儿药物激发试验１０次血标本,用免疫放射计量（ＩＲＭＡ）方法测定ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３,放免方法（ＲＩＡ）测定ＧＨ。结果药物激发试验ＧＨ水平与ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３测定一致。运动激发试验根据运动后ＧＨ水平及身高百分位的情况将６８例分为３组：ＧＨ＜５０μｇ／Ｌ,５０～１００μｇ／Ｌ,＞１００μｇ／Ｌ。ＧＨ＜５０μｇ／Ｌ组１４例,其中１０例身高小于第３百分位,其ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３水平分别是（３９±２０）,（２７４±１２２）,（４２０±２１０）ｎｍｏｌ／Ｌ,低于正常值（Ｐ＜００１）,ＧＨ水平与ＩＧＦ－１,ＩＧＦ－２和ＩＧＦＢＰ－３相符。结论用运动激发试验联合测定ＧＨ、ＩＧＦ－１和ＩＧＦＢＰ－３三项指标可以提高由于ＧＨ－ＩＧＦ轴异常所引起的生长发育迟缓诊断的准确性。     

Developmental pattern of fetal growth hormone,insulin-like growth factor I,growth hormone binding protein and insulin-like growth factor binding protein-3

AIMS—To evaluate the developmental pattern of fetal growth hormone (GH), insulin-like growth factor I (IGF-I), GH binding protein (GHBP) and IGF binding protein-3 (IGF-3); to determine the implications for fetal growth.
METHODS—Serum GH, IGF-I, GHBP and IGFBP-3 were measured in 53 fetuses, 41 aged 20-26 weeks (group A) and 12 aged 31-38 weeks (group B). Fetal blood samples were obtained by direct puncture of the umbilical vein in utero. Fetal blood samples were taken to rule out β thalassaemia, chromosome alterations, mother to fetus transmissible infections, and for maternal rhesus factor. GHBP was determined by gel filtration chromatography of serum incubated overnight with ¹²⁵I-GH. GH, IGF-I and IGFBP-3 were determined by radioimmunoassay.
RESULTS—Fetal serum GH concentrations in group A (median 29 µg/l, range 11-92) were significantly higher (P<0.01) than those of group B (median 16.7 µg/l, range 4.5-29). IGF-I in group A (median 20 µg/l, range 4.1-53.3) was significantly lower (P<0.01) than in group B (median 75.2 µg/l, range 27.8-122.3). Similarly, IGFBP-3 concentrations in group A (median 950 µg/l, range 580-1260) were significantly lower than those of group B (median 1920 µg/l, range 1070-1770). There was no significant difference between GHBP values in group A (median 8.6%, range 6.6-12.6) and group B (median 8.3%, range 6-14.3). Gestational age correlated positively with IGF-I concentrations (P<0.0001) and IGFBP-3 (P<0.0001) and negatively with GH (P<0.0001). GHBP values did not correlate with gestational age. Multiple regression analysis showed a negative correlation between GH:IGF-I ratio and fetal growth indices
CONCLUSIONS—The simultaneous evaluation of fetal GH, IGF-I, IGFBP-3 and GHBP suggests that the GH-IGF-I axis might already be functional in utero. The progressive improvement in the efficiency of this axis in the last part of gestation does not seem to be due to an increase in GH receptors.

     

1型糖尿病儿童血胰岛素样生长因子的变化

目的 探讨中国1型糖尿病病儿血胰岛素样生长因子－1（IGF－1）和胰岛素样生长因子结合蛋白－3（IGFBP－3）的变化。方法 糖尿病组46例,测定胰岛素治疗前、后血IGF－1、IGFBP－3等指标。对照组为正常儿童78例,测定空腹血IGF－1,IGFBP－3。结果 1．糖尿病组胰岛素治疗前血IGF－1和IGFBP－3均低于正常对照组,P＜0．01。经过胰岛素治疗,血IGF－1和IGFBP－3的水平随血糖水平的下降和C－肽水平的升高明显上升,仍低于对照组,P＜0．05。2．糖尿病组使用胰岛素治疗前血IGF－1和IGFBP－3分别与治疗前血糖浓度呈高度负相关关系,P＜0．05。胰岛素治疗前、后血IGF－1与血C－肽水平呈高度正相关关系,P＜0．05。结论 1型糖尿病病儿血IGF－1和TGFBP－3明显下降,青春期前血胰岛素和C－肽可能对IGF－1和IGFBP－3起主要调节作用。