title: Enhanced placental GLUT1 and GLUT3 expression in dexamethasone-induced fetal growth retardation.
abstract: Intrauterine growth retardation (IUGR) increases the risk of developing glucose intolerance and cardiovascular disease in adulthood. Fetal exposure to excess glucocorticoids may contribute to IUGR. Despite the importance of glucose supply for fetal growth, studies on glucose transporter expression in IUGR are few. Two glucose transporters, GLUT1 and GLUT3, are expressed in placenta. In rodent placenta, GLUT1 is replaced by GLUT3 during late gestation. We examined placental GLUT protein expression in 21-day pregnant rats administered dexamethasone (DEX) from day 15 of gestation via osmotic minipump (at doses of 100 or 200 microg/kg body wt. per day). A dose-dependent decline in placental and fetal weight occurred in the DEX groups at day 21. Placental GLUT3 protein expression increased dose-dependently in the DEX groups (by 1.3-fold (n.s) and 2.3-fold (P<0.01), respectively). GLUT1 protein expression also increased dose-dependently in the DEX groups (by 1.6-fold (P<0.05) and 1.9-fold (P<0.01), respectively). In the DEX-treated groups, altered GLUT protein expression occurred in the absence of altered peroxisome proliferator-activated receptor-gamma (PPAR-gamma) protein expression in day 21 placenta; however, PPAR-gamma protein expression in day 21 fetal hearts was greatly suppressed. We conclude that increased placental GLUT1 protein expression may reflect an attempt to increase placental or fetal glucose supply to attenuate the effect of excessive exposure to glucocorticoids to diminish fetal growth, whereas suppression of cardiac PPAR-gamma expression during cardiac development may contribute to the increased risk of developing heart disease found in people of below average birthweight.
authors.affiliation: Department of Diabetes and Metabolic Medicine, Division of General and Developmental Medicine, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary, University of London, London E1 4NS, UK. m.l.langdown@qmw.ac.uk
authors.forename: M L
authors.initials: ML
authors.lastname: Langdown
authors.forename: M C
authors.initials: MC
authors.lastname: Sugden
mesh_terms: D000818:Animals; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005317:Fetal Growth Retardation / Q000139:chemically induced* / Q000378:metabolism; D005333:Fetus; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006321:Heart / Q000196:embryology; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000737:chemistry / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D018160:Receptors, Cytoplasmic and Nuclear; C495679:Slc2a1 protein, rat; C495690:Slc2a3 protein, rat; D014157:Transcription Factors; D003907:Dexamethasone