胰岛素样生长因子与胎儿宫内发育迟缓

1、    胰岛素样生长因子与胎儿宫内发育迟缓        0引言 1IGFs1957年Salmon发现生长激素(growth hormone,GH)是通过硫酸盐因子介导而间接发挥其硫酸盐活性的.该硫酸盐因子就是后来的IGFs,并从那时起开始了对IGFs的研究.随着对这种生长激素依赖因子的多种代谢作用和不被抗胰岛素抗体阻断的活性的认识，统称为促生长因子(somatomedins).在研究其化学结构的同时，提纯了两种相同的物质，促生长因子A和促生长因子C.由于它们与胰岛素的结构相

2、似被称为胰岛素样生长因子,包括IGF-和IGF-.IGF-与以前的促生长因子A和C是完全相同的2.2IGFs与胎儿生长的关系胰岛素与IGF-在早期胚胎发育过程中可能起重要的作用.妊娠期间，母血循环中的IGF-浓度逐渐增加，产后含量迅速降低.胎儿体内IGF-大约于孕15wk左右可检测到.Thiet等4用免疫组化技术证实妊娠19wk22wk胎儿子宫内膜中存在胰岛素、IGF-及其受体，且其分布相同.提示胰岛素及IGF-以自分泌、旁分泌方式在胎儿苗勒氏管发育中起重要作用.脐动脉血和脐静脉血中IGF-及IGFBP-1的浓度相似，二者无明显差别，且与新生儿体质量呈负相关，提示IGF-在母体和新生儿的分泌是

3、各自独立的，IGF-不能通过胎盘.Baker等5研究证实IGF-和IGF-系统在胚胎发育和胎儿生长中起中心作用.这些研究还揭示IGF-和IGF-都是通过IGF-受体来调节胎儿生长的.目前还没有发现IGF-能通过另外的受体产生其它的作用.在对羊的IGFs系统研究6中发现，与人类促生长轴不同，羊的内分泌轴是葡萄糖胰岛素IGF-轴.胎羊的垂体切除术可使新生羊的IGF-水平较正常出生羊的低.有实验证据显示：即能调节胎儿胰岛素释放又能调节胎儿IGF-释放的胎盘葡萄糖转运是胎儿生长调节的一个主要通道.羊胎胰腺切除术可致羊血清IGF-水平显著降低.这些均可通过给胎儿输注葡萄糖或胰岛素得到恢复7.胰岛素和IG

4、F-还是子宫生长和发育所必须的.Shifren等8研究发现孕10wk22wk人类胎儿子宫内有编码IGF-和胰岛素受体，IGF-受体及IGF-受体的mRNA.3IGFs与IUGR4IGFs对IUGR的诊断和治疗作用作者单位：第四军医大学西京医院妇产科陕西西安710033参考文献1 Gluckman PD.The endocrine regulation of fetal growth in late gestation:The role of insulin-like growth factors. J Clin Endocrinol Metab, 1995;80(4):1047-10492 R

5、anke MB,Elmlinger M.Functional role of insulin-like growth factor binding proteins. Horm Res, 1997;48(Suppl 4):9-153 LeRoith D,Werner H,Beitner-Johnson D.Molecular and cellular aspects of the insulin-like growth factor receptor. Endocr Rev ,1995;16(1):143-1634 Thiet MP,Osathanondh R,Yeh J.Localizati

6、on and timing of appearance of insulin,insulin-like growth factor-,and their receptors in the human fetal müllerian tract.Am J Obstet Gynecol,1994;170(1):152-1565 Baker J,Liu JP,Robertson EJ et al. Role of insulin-like growth factor in embryonic and postnatal growth.Cell,1993;75(1):73-826 Kimbl

7、e R,Harding J,Kolbe A.Intraluminal IGF- ameliorates the histological changes of gut atresia in fetal sheep.International Congress of paediatric Surgery and Paediatric Radiology,Melbourne,1995(abstract)7 Oliver MH,Harding JE,Breier BH et al.Fetal insulin-like growth factor(IGF)- and IGF- are regulate

8、d differently by glucose or insulin-like in the sheep fetus. Reprod Fertil Dev，1993;59(2):167-1728 Shifren JL,Osathanondh R,Yeh J. Human fetal ovaries and uteri:developmental expression of genes enconding the insulin,insulin-like growth factor-,and insulin-like growth factor receptors. Fertil Steril

9、 ,1993;59(4):1036-10409 Harding JE,Liu L,Evans PC et al.IGF- alters feto-placental protein and carbohydrate metabolism in fetal sheep. Endocrinology,1994;134:1509-151510 Clark R,Strasser J,McCabe S,et al. Insulin-like growth factor- stimulation of lymphopoiesis. J Clin Invest,1993;92(2):504-50811 Fr

10、anchimont N,Durant D,Canalis E.Interleukin-6 and its soluble receptor regulate the expression of insulin-like growth factor binding protein-5 in osteoblast cultures. Endocrinology,1997; 138(8):3380-338612 Gluckman PD,Harding JE.The physiology and pathophysiology of intrauterine growth retardation. H

11、orm Res,1997;48(Suppl 1):11-1613 Verhaeghe J,Van Bree R,Van Herck E et al. C-peptide,insulin-like growth factors and,insulin-like growth factor binding protein- in umbilical cord serum :correlations with birthweight. Am J Obstet Gynecol,1993;169(1):89-9714 Owens JA,Kind KL,Carbone F et al. Circulati

12、ng insulin-like growth factors-and - and substrates in fetal sheep following restriction of placental growth. J Endocrinol, 1994,140(1):5-1315 Crystal RA,Guidice LC.Insulin-like growth factor binding protein profiles in human fetal sera:ontogeny during gestation and differences in newborns with iUGR

13、 and LGA newborns. In:Spencer EM,ed. Modern concepts of insulin-like growth factors. New York:Elsevier,1991:395-40816 Wang HS,Chard T.The role of insulin-like growth factor-and insulin-like growth factor-binding protein- in the control of human fetal growth. J endocrinol,1992;132(1):11-1917 Unterman

14、 TG,Simmons RA, Glick RP et al. Circulation leves of insulin,insulin-like growth factor-(IGF-),IGF-,and IGF -binding proteins in the small for gestational age fetal rat. Endocrinology,1993;132(1):327-33018 Spencer JAD,Chang TC,Jones J et al. Third trimester fetal growth and umbilical venous blood co

15、ncentrations of IGF-,IGFBP-,and growth hormone at term. Arch Dis Child Fetal Neonatol Ed,1995;73:F87-F9019 Holmes R,Montemagno R,Jones J et al.Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth.Early Hum Dev,1997;49(1):7-1720 Rutanen EM,Pekonen FM, Kinen T et al. Soluble 3