title: Estrogen regulates insulin-like growth factor 1, platelet-derived growth factor A and B, and their receptors in the vascular wall.
abstract: 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.
authors.affiliation: Transplantation Laboratory and Rational Drug Design Programme, Biomedicum, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland. Hanna.Peltonen@Helsinki.Fi
authors.forename: Hanna
authors.initials: H
authors.lastname: Savolainen-Peltonen
authors.forename: Michael
authors.initials: M
authors.lastname: Loubtchenkov
authors.forename: Loubomir
authors.initials: L
authors.lastname: Petrov
authors.forename: Patrice
authors.initials: P
authors.lastname: Delafontaine
authors.forename: Pekka
authors.initials: P
authors.lastname: Häyry
mesh_terms: D000818:Animals; D001011:Aorta / Q000473:pathology; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000378:metabolism*; D004958:Estradiol / Q000008:administration & dosage / Q000494:pharmacology*; D006652:Histological Techniques; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014018:Tissue Distribution
chemical_list: D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1; D020797:Receptor, Platelet-Derived Growth Factor beta