胰岛素样生长因子(IGFs)是一类既具有促进细胞分化和增殖,又具有胰岛素样作用的多肽,它们可以作为一种激素发挥全身性的影响,也可以作为自分泌/旁分泌因子在局部产生作用。IGFs通过其配体与细胞表面的受体结合发挥作用,当受体被激活后,它触发酪氨酸蛋白激酶激活从而开始一系列级联反应,最终在不同的细胞类型出现不同的生物学效应。线性生长是指身长/身高的生长,由基因、环境、营养、激素和许多生长因子共同调节完成,环境、营养等宏观因素对它的影响通过影响一系列促生长激素、生长因子等微观因素的作用来实现。线性生长是一个持续的过程,在这个过程中IGFs系统起着重要作用。
转贴于2.6 IGFII/M6PR
IGFII/M6PR在维持正常线性生长中有作用。IGFII/M6PR主要是一种清除受体,与IGFII结合后降低循环中IGFII的水平,从而维持血中IGFII的正常需要量[8]。如IGFII/M6PR基因敲除鼠出现胎儿“过生长”(Overgrowth),出生体重为正常鼠的135%。其机制是IGFII/M6PR基因缺失影响了血中IGFII的清除率,IGFII水平升高而出现“过生长”[6]。
IGFII/M6PR在维持正常线性生长中有作用。IGFII/M6PR主要是一种清除受体,与IGFII结合后降低IGFII/M6PR在维持正常线性生长中有作用。IGFII/M6PR主要是一种清除受体,与IGFII结合后降低循环中IGFII的水平,从而维持血中IGFII的正常需要量[8]。如IGFII/M6PR基因敲除鼠出现胎儿“过生长”(Overgrowth),出生体重为正常鼠的135%。其机制是IGFII/M6PR基因缺失影响了血中IGFII的清除率,IGFII水平升高而出现“过生长”[6]。
2.7 IGFBPs
IGFBPs主要在肝产生,起调节IGFs生物利用度的作用。所以他们也参与线性生长的调节。如IGFBP1在胎儿生长中起抑制作用,在IUGR(宫内生长迟缓)新生儿的血中IGFBP1明显升高[12];在IGFBP1基因过表达鼠,其出生体重下降[21];具体机制还不清楚,可能是高水平的IGFBP1使生物池中可用的IGFI的量减少所导致[22]。IGFBP2在体内通过内分泌或自分泌抑制IGFI的代谢作用,减少出生后体重的增长,在IGFI基因过表达鼠体重增加约20%,而IGFBP2基因过表达鼠生后体重明显减少[23];IGFBP2与出生体重、身长负相关[13]。IGFBP3在生长中起促进作用,有实验报道IGFBP3与出生体重正相关;在生后,IGFBP3同样促进生长。这可能是由于IGFBP3是血循环中IGFI最主要的载体蛋白,在转运IGFI、延长其半衰期、调节IGFI与受体作用等方面发挥着重要作用,即IGFBP3的促生长作用是通过影响IGFI的作用来实现[24]。IGFBP4是IGFBPs中分子量最小的,是一细胞增殖抑制因子。它结合IGFI和IGFII的方式相似,通过抑制他们的生物学作用来抑制生长[25]。IGFBP5是最保守的,在各物种间变化不大,除了影响IGFI和IGFII的作用外,还具能独立促进骨的生长[26]。IGFBP6已被证明抑制多种细胞的增殖,在IGFBP6转基因鼠,出生体重明显降低;IGFBP6与IGFII亲和力最强,可能是通过影响IGFII的生物利用度来抑制生长[27]。
总之,IGFs系统的各成分都参与了线性生长的调节。在这个过程中,它们各自独立或互相依赖或影响其他生长调节因子作用,但具体机制还不太清楚。随着分子生物学水平研究的深入,IGFs系统在线性生长中的确切作用机制将明确,这无论对基础研究还是临床应用都有重要意义。
循环中IGFII的水平,从而维持血中IGFII的正常需要量[8]。如IGFII/M6PR基因敲除鼠出现胎儿“过生长”(Overgrowth),出生体重为正常鼠的135%。其机制是IGFII/M6PR基因缺失影响了血中IGFII的清除率,IGFII水平升高而出现“过生长”[6]。
2.7 IGFBPs
IGFBPs主要在肝产生,起调节IGFs生物利用度的作用。所以他们也参与线性生长的调节。如IGFBP1在胎儿生长中起抑制作用,在IUGR(宫内生长迟缓)新生儿的血中IGFBP1明显升高[12];在IGFBP1基因过表达鼠,其出生体重下降[21];具体机制还不清楚,可能是高水平的IGFBP1使生物池中可用的IGFI的量减少所导致[22]。IGFBP2在体内通过内分泌或自分泌抑制IGFI的代谢作用,减少出生后体重的增长,在IGFI基因过表达鼠体重增加约20%,而IGFBP2基因过表达鼠生后体重明显减少[23];IGFBP2与出生体重、身长负相关[13]。IGFBP3在生长中起促进作用,有实验报道IGFBP3与出生体重正相关;在生后,IGFBP3同样促进生长。这可能是由于IGFBP3是血循环中IGFI最主要的载体蛋白,在转运IGFI、延长其半衰期、调节IGFI与受体作用等方面发挥着重要作用,即IGFBP3的促生长作用是通过影响IGFI的作用来实现[24]。IGFBP4是IGFBPs中分子量最小的,是一细胞增殖抑制因子。它结合IGFI和IGFII的方式相似,通过抑制他们的生物学作用来抑制生长[25]。IGFBP5是最保守的,在各物种间变化不大,除了影响IGFI和IGFII的作用外,还具能独立促进骨的生长[26]。IGFBP6已被证明抑制多种细胞的增殖,在IGFBP6转基因鼠,出生体重明显降低;IGFBP6与IGFII亲和力最强,可能是通过影响IGFII的生物利用度来抑制生长[27]。
总之,IGFs系统的各成分都参与了线性生长的调节。在这个过程中,它们各自独立或互相依赖或影响其他生长调节因子作用,但具体机制还不太清楚。随着分子生物学水平研究的深入,IGFs系统在线性生长中的确切作用机制将明确,这无论对基础研究还是临床应用都有重要意义。
【参考文献】 IGFII/M6PR在维持正常线性生长中有作用。IGFII/M6PR主要是一种清除受体,与IGFII结合后降低循环中IGFII的水平,从而维持血中IGFII的正常需要量[8]。如IGFII/M6PR基因敲除鼠出现胎儿“过生长”(Overgrowth),出生体重为正常鼠的135%。其机制是IGFII/M6PR基因缺失影响了血中IGFII的清除率,IGFII水平升高而出现“过生长”[6]。
2.7 IGFBPs
IGFBPs主要在肝产生,起调节IGFs生物利用度的作用。所以他们也参与线性生长的调节。如IGFBP1在胎儿生长中起抑制作用,在IUGR(宫内生长迟缓)新生儿的血中IGFBP1明显升高[12];在IGFBP1基因过表达鼠,其出生体重下降[21];具体机制还不清楚,可能是高水平的IGFBP1使生物池中可用的IGFI的量减少所导致[22]。IGFBP2在体内通过内分泌或自分泌抑制IGFI的代谢作用,减少出生后体重的增长,在IGFI基因过表达鼠体重增加约20%,而IGFBP2基因过表达鼠生后体重明显减少[23];IGFBP2与出生体重、身长负相关[13]。IGFBP3在生长中起促进作用,有实验报道IGFBP3与出生体重正相关;在生后,IGFBP3同样促进生长。这可能是由于IGFBP3是血循环中IGFI最主要的载体蛋白,在转运IGFI、延长其半衰期、调节IGFI与受体作用等方面发挥着重要作用,即IGFBP3的促生长作用是通过影响IGFI的作用来实现[24]。IGFBP4是IGFBPs中分子量最小的,是一细胞增殖抑制因子。它结合IGFI和IGFII的方式相似,通过抑制他们的生物学作用来抑制生长[25]。IGFBP5是最保守的,在各物种间变化不大,除了影响IGFI和IGFII的作用外,还具能独立促进骨的生长[26]。IGFBP6已被证明抑制多种细胞的增殖,在IGFBP6转基因鼠,出生体重明显降低;IGFBP6与IGFII亲和力最强,可能是通过影响IGFII的生物利用度来抑制生长[27]。
总之,IGFs系统的各成分都参与了线性生长的调节。在这个过程中,它们各自独立或互相依赖或影响其他生长调节因子作用,但具体机制还不太清楚。随着分子生物学水平研究的深入,IGFs系统在线性生长中的确切作用机制将明确,这无论对基础研究还是临床应用都有重要意义。
【】
2.2.6 IGFII/M6PR
IGFII/M6PR在维持正常线性生长中有作用。IGFII/M6PR主要是一种清除受体,与IGFII结合后降低循环中IGFII的水平,从而维持血中IGFII的正常需要量[8]。如IGFII/M6PR基因敲除鼠出现胎儿“过生长”(Overgrowth),出生体重为正常鼠的135%。其机制是IGFII/M6PR基因缺失影响了血中IGFII的清除率,IGFII水平升高而出现“过生长”[6]。
2.7 IGFBPs
IGFBPs主要在肝产生,起调节IGFs生物利用度的作用。所以他们也参与线性生长的调节。如IGFBP1在胎儿生长中起抑制作用,在IUGR(宫内生长迟缓)新生儿的血中IGFBP1明显升高[12];在IGFBP1基因过表达鼠,其出生体重下降[21];具体机制还不清楚,可能是高水平的IGFBP1使生物池中可用的IGFI的量减少所导致[22]。IGFBP2在体内通过内分泌或自分泌抑制IGFI的代谢作用,减少出生后体重的增长,在IGFI基因过表达鼠体重增加约20%,而IGFBP2基因过表达鼠生后体重明显减少[23];IGFBP2与出生体重、身长负相关[13]。IGFBP3在生长中起促进作用,有实验报道IGFBP3与出生体重正相关;在生后,IGFBP3同样促进生长。这可能是由于IGFBP3是血循环中IGFI最主要的载体蛋白,在转运IGFI、延长其半衰期、调节IGFI与受体作用等方面发挥着重要作用,即IGFBP3的促生长作用是通过影响IGFI的作用来实现[24]。IGFBP4是IGFBPs中分子量最小的,是一细胞增殖抑制因子。它结合IGFI和IGFII的方式相似,通过抑制他们的生物学作用来抑制生长[25]。IGFBP5是最保守的,在各物种间变化不大,除了影响IGFI和IGFII的作用外,还具能独立促进骨的生长[26]。IGFBP6已被证明抑制多种细胞的增殖,在IGFBP6转基因鼠,出生体重明显降低;IGFBP6与IGFII亲和力最强,可能是通过影响IGFII的生物利用度来抑制生长[27]。
总之,IGFs系统的各成分都参与了线性生长的调节。在这个过程中,它们各自独立或互相依赖或影响其他生长调节因子作用,但具体机制还不太清楚。随着分子生物学水平研究的深入,IGFs系统在线性生长中的确切作用机制将明确,这无论对基础研究还是临床应用都有重要意义。
【参考文献】
[1] Laron Z. IGF1 and insulin as growth hormones [J]. Novartis Found Symp, 2004, 262: 5677.
[2] Drop SL, Schuller AG, LindenberghKortleve DJ, et al. Structural aspects of the IGFBP family [J]. Growth Regul, 1992, 2(2): 6979.
[3] Phillip M, Moran O, Lazar L. Growth without growth hormone [J]. J Pediatr Endocr Met, 2002, 15(S5): 12671272.
[4] Srinivasan S, Waters MJ, Rowland JE. Hypefinsulinism and overgrowth without obesity [J]. Arch Dis Child, 2003, 88(4): 332334.
[5] 梁立阳, 杜敏联, 李燕虹, 等. 单纯性肥胖儿童血清胰岛素、胰岛素样生长因子1及其结合蛋白3与生长的关系[J]. 中山大学学报(医学科学版), 2004, 25(S3): 131133.
[6] D’Ercole AJ. Mechanisms of in utero overgrowth [J]. Acta Paediatr, 1999, 88(428): 3136.
[7] Verhaeghe J, Billen J, Giudice LC. Insulinlike growth factor binding protein1 in umbilical artery and vein of term fetuses with signs suggestive of distress during labor [J]. J Endocrinol, 2001, 170(3): 585590.
[8] Gluckman PD, Pinal CS. Regulation of fetal growth by the somatotrophic axis [J]. J Nutr, 2003, 133(S5): 17411746.
[9] Salmon WD Jr, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro [J]. J Lab Clin Med, 1957, 49(6): 825836.
[10] Laron Z. Insulinlike growth factor 1 (IGF1): a growth hormone [J]. Mol Pathol, 2001, 54(5): 311316.
[11] Liu JP, Baker J, Perkins AS, et al. Mice carrying null mutations of the enes encoding insulinlike growth factor I (Igf1) and type 1 IGF receptor (Igf1r) [J]. Cell, 1993, 75(1): 5972.
[12] Verhaeghe J, Van Herck E, Billen J, et al. Regulation of insulinlike growth factorI and insulinlike growth factor binding protein1 concentrations in preterm fetuses [J]. Am J Obstet Gynecol, 2003, 188(2): 485491.
[13] Lo HC, Tsao LY, Hsu WY, et al. Relation of cord serum levels of growth hormone, insulinlike growth factors, insulinlike growth factor binding proteins, leptin, and interleukin6 with birth weight, birth length, and head circumference in term and preterm neonates [J]. Nutrition, 2002, 18(78): 604608.
[14] Lupu F, Terwilliger JD, Lee K, et al. A roles of growth hormone and insulinlike growth factor 1 in mouse postnatal growth [J]. Dev Biol, 2001, 229(1): 141162.
[15] Ohlsson C, Sjogren K, Jansson JO, et al. The relative importance of endocrine versus autocrine/paracrine insulinlike growth factorI in the regulation of body growth [J]. Pediatr Nephrol, 2000, 14(7): 541543.
[16] Wang J, Zhou J, Bondy CA. Igf1 promotes longitudinal bone growth by insulinlike actions augmenting chondrocyte hypertrophy [J]. FASEB J, 1999, 13(14): 19851990.
[17] Wallenius K, Sjogren K, Peng XD, et al. Liverderived IGFI regulates GH secretion at the pituitary level in mice [J]. Endocrinology, 2001, 142(11): 47624770.
[18] Robson H, Siebler T, Shalet SM, et al. Interactions between GH, IGFI, Glucocorticoids, and Thyroid Hormones during Skeletal Growth [J]. Pediatr Res, 2002, 52(2): 137147.
[19] Pantaleon M, Jericho H, Rabnott G, et al. The role of insulinlike growth factor II and its receptor in mouse preimplantation development [J]. Reprod Fertil Dev, 2003, 15(12): 3745.
[20] Mohan S, Richman C, Guo R, et al. Insulinlike growth factor regulates peak bone mineral density in mice by both growth hormonedependent and independent mechanisms [J]. Endocrinology, 2003, 144(3): 929936.
[21] Sakai K, D’Ercole AJ, Murphy LJ, et al. Physiological differences in insulinlike growth factor binding protein1 (IGFBP1) phosphorylation in IGFBP1 transgenic mice [J]. Diabetes, 2001, 50(1): 3238.
[22] Frystyk J, Hojlund K, Nyborg Rasmussen KN, et al. Development and clinical evaluation of a novel immunoassay for the binary complex of IGFI and IGFbinding protein1 in human serum [J]. J Clin Endocri Met, 2002, 87(1): 260266.
[23] Hoeflich A, Wu M, Mohan S, et al. Overexpression of insulinlike growth factorbinding protein2 in transgenic mice reduces postnatal body weight gain [J]. Endocrinology, 1999, 140(12): 54885496.
[24] Yan X, Forbes BE, McNeil KA, et al. Role of N and Cterminal residues of insulinlike growth factor (IGF)binding protein3 in regulating IGF complex formation and receptor activation [J]. J Biol Chem, 2004, 17, 279(51): 5323253240.
[25] Zhou R, Diehl D, Hoeflich A, et al. IGFbinding protein4: biochemical characteristics and functional consequences [J]. J Endocrinol, 2003, 178(2): 177193.
[26] Miyakoshi N, Richman C, Kasukawa YJ, et al. Evidence that IGFbinding protein5 functions as a growth factor [J]. J Clin Invest, 2001, 107(1): 7381.
[27] Bienvenu G, Seurin D, Grellier P, et al. Insulinlike growth factor binding protein6 transgenic mice: postnatal growth, brain development, and reproduction abnormalities [J]. Endocrinology, 2004, 145(5): 24122420.
转贴于 中国论文下载中心 http://www.7 IGFBPs
2.6 IGFII/M6PR
IGFII/M6PR在维持正常线性生长中有作用。IGFII/M6PR主要是一种清除受体,与IGFII结合后降低循环中IGFII的水平,从而维持血中IGFII的正常需要量[8]。如IGFII/M6PR基因敲除鼠出现胎儿“过生长”(Overgrowth),出生体重为正常鼠的135%。其机制是IGFII/M6PR基因缺失影响了血中IGFII的清除率,IGFII水平升高而出现“过生长”[6]。
2.7 IGFBPs
IGFBPs主要在肝产生,起调节IGFs生物利用度的作用。所以他们也参与线性生长的调节。如IGFBP1在胎儿生长中起抑制作用,在IUGR(宫内生长迟缓)新生儿的血中IGFBP1明显升高[12];在IGFBP1基因过表达鼠,其出生体重下降[21];具体机制还不清楚,可能是高水平的IGFBP1使生物池中可用的IGFI的量减少所导致[22]。IGFBP2在体内通过内分泌或自分泌抑制IGFI的代谢作用,减少出生后体重的增长,在IGFI基因过表达鼠体重增加约20%,而IGFBP2基因过表达鼠生后体重明显减少[23];IGFBP2与出生体重、身长负相关[13]。IGFBP3在生长中起促进作用,有实验报道IGFBP3与出生体重正相关;在生后,IGFBP3同样促进生长。这可能是由于IGFBP3是血循环中IGFI最主要的载体蛋白,在转运IGFI、延长其半衰期、调节IGFI与受体作用等方面发挥着重要作用,即IGFBP3的促生长作用是通过影响IGFI的作用来实现[24]。IGFBP4是IGFBPs中分子量最小的,是一细胞增殖抑制因子。它结合IGFI和IGFII的方式相似,通过抑制他们的生物学作用来抑制生长[25]。IGFBP5是最保守的,在各物种间变化不大,除了影响IGFI和IGFII的作用外,还具能独立促进骨的生长[26]。IGFBP6已被证明抑制多种细胞的增殖,在IGFBP6转基因鼠,出生体重明显降低;IGFBP6与IGFII亲和力最强,可能是通过影响IGFII的生物利用度来抑制生长[27]。
总之,IGFs系统的各成分都参与了线性生长的调节。在这个过程中,它们各自独立或互相依赖或影响其他生长调节因子作用,但具体机制还不太清楚。随着分子生物学水平研究的深入,IGFs系统在线性生长中的确切作用机制将明确,这无论对基础研究还是临床应用都有重要意义。
【参考文献】
[1] Laron Z. IGF1 and insulin as growth hormones [J]. Novartis Found Symp, 2004, 262: 5677.
[2] Drop SL, Schuller AG, LindenberghKortleve DJ, et al. Structural aspects of the IGFBP family [J]. Growth Regul, 1992, 2(2): 6979.
[3] Phillip M, Moran O, Lazar L. Growth without growth hormone [J]. J Pediatr Endocr Met, 2002, 15(S5): 12671272.
[4] Srinivasan S, Waters MJ, Rowland JE. Hypefinsulinism and overgrowth without obesity [J]. Arch Dis Child, 2003, 88(4): 332334.
[5] 梁立阳, 杜敏联, 李燕虹, 等. 单纯性肥胖儿童血清胰岛素、胰岛素样生长因子1及其结合蛋白3与生长的关系[J]. 中山大学学报(医学科学版), 2004, 25(S3): 131133.
[6] D’Ercole AJ. Mechanisms of in utero overgrowth [J]. Acta Paediatr, 1999, 88(428): 3136.
[7] Verhaeghe J, Billen J, Giudice LC. Insulinlike growth factor binding protein1 in umbilical artery and vein of term fetuses with signs suggestive of distress during labor [J]. J Endocrinol, 2001, 170(3): 585590.
[8] Gluckman PD, Pinal CS. Regulation of fetal growth by the somatotrophic axis [J]. J Nutr, 2003, 133(S5): 17411746.
[9] Salmon WD Jr, Daughaday WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro [J]. J Lab Clin Med, 1957, 49(6): 825836.
[10] Laron Z. Insulinlike growth factor 1 (IGF1): a growth hormone [J]. Mol Pathol, 2001, 54(5): 311316.
[11] Liu JP, Baker J, Perkins AS, et al. Mice carrying null mutations of the enes encoding insulinlike growth factor I (Igf1) and type 1 IGF receptor (Igf1r) [J]. Cell, 1993, 75(1): 5972.
[12] Verhaeghe J, Van Herck E, Billen J, et al. Regulation of insulinlike growth factorI and insulinlike growth factor binding protein1 concentrations in preterm fetuses [J]. Am J Obstet Gynecol, 2003, 188(2): 485491.
[13] Lo HC, Tsao LY, Hsu WY, et al. Relation of cord serum levels of growth hormone, insulinlike growth factors, insulinlike growth factor binding proteins, leptin, and interleukin6 with birth weight, birth length, and head circumference in term and preterm neonates [J]. Nutrition, 2002, 18(78): 604608.
[14] Lupu F, Terwilliger JD, Lee K, et al. A roles of growth hormone and insulinlike growth factor 1 in mouse postnatal growth [J]. Dev Biol, 2001, 229(1): 141162.
[15] Ohlsson C, Sjogren K, Jansson JO, et al. The relative importance of endocrine versus autocrine/paracrine insulinlike growth factorI in the regulation of body growth [J]. Pediatr Nephrol, 2000, 14(7): 541543.
[16] Wang J, Zhou J, Bondy CA. Igf1 promotes longitudinal bone growth by insulinlike actions augmenting chondrocyte hypertrophy [J]. FASEB J, 1999, 13(14): 19851990.
[17] Wallenius K, Sjogren K, Peng XD, et al. Liverderived IGFI regulates GH secretion at the pituitary level in mice [J]. Endocrinology, 2001, 142(11): 47624770.
[18] Robson H, Siebler T, Shalet SM, et al. Interactions between GH, IGFI, Glucocorticoids, and Thyroid Hormones during Skeletal Growth [J]. Pediatr Res, 2002, 52(2): 137147.
[19] Pantaleon M, Jericho H, Rabnott G, et al. The role of insulinlike growth factor II and its receptor in mouse preimplantation development [J]. Reprod Fertil Dev, 2003, 15(12): 3745.
[20] Mohan S, Richman C, Guo R, et al. Insulinlike growth factor regulates peak bone mineral density in mice by both growth hormonedependent and independent mechanisms [J]. Endocrinology, 2003, 144(3): 929936.
[21] Sakai K, D’Ercole AJ, Murphy LJ, et al. Physiological differences in insulinlike growth factor binding protein1 (IGFBP1) phosphorylation in IGFBP1 transgenic mice [J]. Diabetes, 2001, 50(1): 3238.
[22] Frystyk J, Hojlund K, Nyborg Rasmussen KN, et al. Development and clinical evaluation of a novel immunoassay for the binary complex of IGFI and IGFbinding protein1 in human serum [J]. J Clin Endocri Met, 2002, 87(1): 260266.
[23] Hoeflich A, Wu M, Mohan S, et al. Overexpression of insulinlike growth factorbinding protein2 in transgenic mice reduces postnatal body weight gain [J]. Endocrinology, 1999, 140(12): 54885496.
[24] Yan X, Forbes BE, McNeil KA, et al. Role of N and Cterminal residues of insulinlike growth factor (IGF)binding protein3 in regulating IGF complex formation and receptor activation [J]. J Biol Chem, 2004, 17, 279(51): 5323253240.
[25] Zhou R, Diehl D, Hoeflich A, et al. IGFbinding protein4: biochemical characteristics and functional consequences [J]. J Endocrinol, 2003, 178(2): 177193.
[26] Miyakoshi N, Richman C, Kasukawa YJ, et al. Evidence that IGFbinding protein5 functions as a growth factor [J]. J Clin Invest, 2001, 107(1): 7381.
[27] Bienvenu G, Seurin D, Grellier P, et al. Insulinlike growth factor binding protein6 transgenic mice: postnatal growth, brain development, and reproduction abnormalities [J]. Endocrinology, 2004, 145(5): 24122420.
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IGFBPs主要在肝产生,起调节IGFs生物利用度的作用。所以他们也参与线性生长的调节。如IGFBP1在胎儿生长中起抑制作用,在IUGR(宫内生长迟缓)新生儿的血中IGFBP1明显升高[12];在IGFBP1基因过表达鼠,其出生体重下降[21];具体机制还不清楚,可能是高水平的IGFBP1使生物池中可用的IGFI的量减少所导致[22]。IGFBP2在体内通过内分泌或自分泌抑制IGFI的代谢作用,减少出生后体重的增长,在IGFI基因过表达鼠体重增加约20%,而IGFBP2基因过表达鼠生后体重明显减少[23];IGFBP2与出生体重、身长负相关[13]。IGFBP3在生长中起促进作用,有实验报道IGFBP3与出生体重正相关;在生后,IGFBP3同样促进生长。这可能是由于IGFBP3是血循环中IGFI最主要的载体蛋白,在转运IGFI、延长其半衰期、调节IGFI与受体作用等方面发挥着重要作用,即IGFBP3的促生长作用是通过影响IGFI的作用来实现[24]。IGFBP4是IGFBPs中分子量最小的,是一细胞增殖抑制因子。它结合IGFI和IGFII的方式相似,通过抑制他们的生物学作用来抑制生长[25]。IGFBP5是最保守的,在各物种间变化不大,除了影响IGFI和IGFII的作用外,还具能独立促进骨的生长[26]。IGFBP6已被证明抑制多种细胞的增殖,在IGFBP6转基因鼠,出生体重明显降低;IGFBP6与IGFII亲和力最强,可能是通过影响IGFII的生物利用度来抑制生长[27]。
总之,IGFs系统的各成分都参与了线性生长的调节。在这个过程中,它们各自独立或互相依赖或影响其他生长调节因子作用,但具体机制还不太清楚。随着分子生物学水平研究的深入,IGFs系统在线性生长中的确切作用机制将明确,这无论对基础研究还是临床应用都有重要意义。
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[20] Mohan S, Richman C, Guo R, et al. Insulinlike growth factor regulates peak bone mineral density in mice by both growth hormonedependent and independent mechanisms [J]. Endocrinology, 2003, 144(3): 929936.
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[26] Miyakoshi N, Richman C, Kasukawa YJ, et al. Evidence that IGFbinding protein5 functions as a growth factor [J]. J Clin Invest, 2001, 107(1): 7381.
[27] Bienvenu G, Seurin D, Grellier P, et al. Insulinlike growth factor binding protein6 transgenic mice: postnatal growth, brain development, and reproduction abnormalities [J]. Endocrinology, 2004, 145(5): 24122420.
转贴于 中国论文下载中心 http://www. 中国论文下载中心 http://www.