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Estrogen regulates insulin-like growth factor 1, platelet-derived growth factor A and B, and their receptors in the vascular wall.

Authors: Savolainen-Peltonen, H  Loubtchenkov, M  Petrov, L  Delafontaine, P  Hayry, P 
Citation: Savolainen-Peltonen H, etal., Transplantation. 2004 Jan 15;77(1):35-42.
Pubmed: (View Article at PubMed) PMID:14724432
DOI: Full-text: DOI:10.1097/01.TP.0000101496.53362.A0

BACKGROUND: Peptide growth factors induce vascular smooth muscle cell (SMC) proliferation and migration after vascular injury, leading to arterial stenosis. Estrogen provides vasculoprotective effects by regulating endothelial and vascular SMC function. METHODS: We performed aortic denudations in male Wistar rats. One group received 17beta-estradiol, 0.25 mg/kg per day subcutaneously, and the other group vehicle. Growth factor and receptor mRNA in the aorta wall was quantitated at 15 minutes, 3 days, and 7 days after denudation. Western blotting and immunohistochemistry were used to quantify and localize the protein. RESULTS: Aortic injury caused SMC proliferation in the intima and media, indicated by an increase in the number of intimal nuclei and area. Quantitative reverse-transcriptase polymerase chain reaction and Western blotting showed concomitant up-regulation of insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-B, and PDGF-receptor (R)alpha. 17beta-estradiol significantly inhibited SMC proliferation and intimal thickening. Similarly, estrogen administration completely suppressed IGF-1 mRNA (P=0.004) and protein but had no effect on IGF-1R. Estrogen had virtually no effect on PDGF-A mRNA or protein levels; however, on day 7, it inhibited PDGF-Ralpha mRNA by 74% (P=0.005) and protein by 67%. On day 7, it also inhibited PDGF-B mRNA expression by 36% (P=0.04) but had little effect on protein. PDGF-Rbeta expression was unaffected by estrogen. Estradiol treatment reduced immunoreactivity of IGF-1, PDGF-A, PDGF-Ralpha, and PDGF-B in vascular lesions, whereas no changes were seen with respect to IGF-1R and PDGF-Rbeta. CONCLUSIONS: Our findings demonstrate that estrogen regulates IGF-1, PDGF-A, PDGF-B, and PDGF-Ralpha, which may be related to the vasculoprotective effect of estrogen, but has no effect on IGF-1R or PDGF-Rbeta.


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CRRD Object Information
CRRD ID: 2292171
Created: 2008-04-11
Species: All species
Last Modified: 2008-04-11
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.