Changes in IGF-I and -II, IGF binding protein, and IGF receptor transcript abundance after uterine artery ligation.
Altered IGF activity may be one mechanism involved in the pathogenesis of intrauterine growth retardation (IUGR). We assessed the expression of IGF, IGF binding protein (IGFBP), and IGF receptor transcripts in liver, carcass, and placenta of fetal rats with IUGR resulting from unilateral uterine artery ligation. We found that uterine artery ligation on d 17 of gestation resulted in reduced body weight, liver weight, and placental weight on d 20 in the fetuses from the ligated uterine horn (UA-lig) compared with those from the opposite, nonligated uterine horn (UA-nonlig) and those from dams with no surgery or anesthesia. As assessed by solution hybridization, UA-lig fetuses exhibited significantly higher hepatic IGFBP-1, IGFBP-2, and IGF-II transcript abundance than UA-nonlig controls (increased 110, 50, and 31%, respectively). The only major difference among groups in carcass and placenta mRNA abundance was a 44% decrease in placental IGF-II expression in UA-lig pups compared with pups from dams that had had no surgery or anesthesia. Serum IGFBP, analyzed by ligand blot, showed a 2.4-fold increase in the doublet IGFBP-1/-2 band in UA-lig fetuses. Serum immunoreactive IGFBP-2 was unchanged among the groups, indicating that IGFBP-1 accounted for the increase in doublet intensity. Our results suggest that increased serum IGFBP-1 concentrations may decrease IGF activity in serum and thus inhibit IGF-stimulated cell proliferation or, by crossing the endothelial border, inhibit the activity of locally produced IGF. Decreased IGF-II expression in placenta also may contribute to decreased placental growth and, in turn, to IUGR.(ABSTRACT TRUNCATED AT 250 WORDS)
Price
W A
WA
Department of Pediatrics, University of North Carolina, Chapel Hill 27599.
Rong
L
L
Stiles
A D
AD
D'Ercole
A J
AJ
D000818:Animals; D003250:Constriction; D005317:Fetal Growth Retardation / Q000378:metabolism; D005333:Fetus / Q000098:blood supply / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D009929:Organ Size; D010920:Placenta / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D017527:Receptor, IGF Type 2 / Q000378:metabolism*
D012333:RNA, Messenger; D017527:Receptor, IGF Type 2; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1