生长受限胎鼠中胰岛素样生长因子受体-1和胰岛素受体的胎盘表达

Placental expression of insulin-like growth factor receptor-1 and insulin receptor in the growth-restricted fetal rat.

作者信息

Reid Gregory J, Flozak Annette S, Simmons Rebecca A

机构信息

Department of Obstetrics and Gynecology, Northwestern University Medical School, Children's Memorial Hospital, Chicago, Illinois, USA.

出版信息

J Soc Gynecol Investig. 2002 Jul-Aug;9(4):210-4.

PMID:12113879

Abstract

OBJECTIVE

The type 1 insulin-like growth factor receptor (IGF-R1), which resembles the insulin receptor (INS-R), is expressed abundantly in the placenta. The regulation of fetal growth by IGFs and insulin might reflect their actions on the placenta. This study compared the placental expression of IGF-R1 and INS-R in growth-restricted and normal pregnancies.

METHODS

Fetal growth restriction was produced in Sprague-Dawley rats by bilateral ligation of the uterine artery on day 19 (term = 21.5 days). Fetuses were delivered by hysterotomy on day 20, and placental samples were frozen. Fetuses that had been subjected to a sham operation of maternal laparotomy without uterine artery manipulation were studied as matched controls. IGF-R1 and INS-R message was assessed by reverse transcription and polymerase chain reaction amplification of extracted placental RNA. The receptors also were assessed by Western blotting of extracted placental protein. Measurements for the growth-restricted group were expressed as a multiple of that of the matched sham litter.

RESULTS

Placental IGF-R1 messenger RNA (mRNA) level was significantly lower in the growth-restricted fetuses (0.66 x sham [0.47-0.93], P <.05), but INS-R mRNA was not different (0.89 x sham [0.63-1.3], P >.5). IGF-R1 protein transcript was similarly reduced in the growth-restricted fetuses (0.78 x sham [0.69-0.88], P <.005), but the INS-R protein transcript was not (0.98 x sham [0.69-1.4], P >.8). Birth weights were significantly less in the growth-restricted group (3.06 +/- 0.07 versus 3.29 +/- 0.06 g, P =.016); placental weights were not (0.54 +/- 0.02 versus 0.54 +/- 0.02 g, P =.90).

CONCLUSIONS

The placenta responds to decreased nutrient delivery with decreased expression of IGF-R1. This would reduce the growth-promoting effects of insulin-like growth factors, which include augmentation of placental lactogen production and glucose and amino acid transport. INS-R was unaffected, which suggests that placental response to insulin is less important than its response to insulin-like growth factors in growth restriction.

摘要

目的

1型胰岛素样生长因子受体（IGF-R1）与胰岛素受体（INS-R）相似，在胎盘中大量表达。胰岛素样生长因子（IGFs）和胰岛素对胎儿生长的调节可能反映了它们对胎盘的作用。本研究比较了生长受限妊娠和正常妊娠中IGF-R1和INS-R的胎盘表达情况。

方法

在妊娠第19天（足月为21.5天）通过双侧结扎子宫动脉在Sprague-Dawley大鼠中诱导胎儿生长受限。在第20天通过子宫切开术娩出胎儿，并将胎盘样本冷冻。对接受了母体剖腹术假手术但未进行子宫动脉操作的胎儿作为匹配对照进行研究。通过对提取的胎盘RNA进行逆转录和聚合酶链反应扩增来评估IGF-R1和INS-R信息。还通过对提取的胎盘蛋白进行蛋白质印迹法来评估受体。生长受限组的测量值表示为匹配假手术窝仔测量值的倍数。

结果

生长受限胎儿的胎盘IGF-R1信使核糖核酸（mRNA）水平显著降低（0.66×假手术组[0.47 - 0.93]，P <.05），但INS-R mRNA无差异（0.89×假手术组[0.63 - 1.3]，P >.5）。生长受限胎儿的IGF-R1蛋白转录物同样减少（0.78×假手术组[0.69 - 0.88]，P <.005），但INS-R蛋白转录物未减少（0.98×假手术组[0.69 - 1.4]，P >.8）。生长受限组的出生体重显著较低（3.06±0.07 vs 3.29±0.06 g，P =.016）；胎盘重量无差异（0.54±0.02 vs 0.54±0.02 g，P =.90）。