Placental glucose transporter expression is regulated by glucocorticoids.
Although glucocorticoids play important roles in development and fetal programming, they are widely used for treatment of a variety of diseases during pregnancy. In various tissues, glucocorticoids down-regulate glucose transport systems; however, their effects on glucose transporters in the placenta are unknown. In the present study, the glucose carrier proteins GLUT1 and GLUT3 were localized in the trophoblast and endothelium of the human, rat, and mouse placenta. Subsequently, it was investigated whether glucocorticoids affect messenger ribonucleic acid and protein expression of these molecules by Northern and Western blotting using 1) human term placental trophoblast cells cultured in the presence or absence of 0.5, 5, and 50 micromol/L triamcinolone; 2) placentas of rats that received a single i.p. dose of 0.38 mg/kg triamcinolone; and 3) placentas of transgenic mice bearing an antisense glucocorticoid receptor gene construct. In all of these systems, both glucose transporters were significantly down-regulated (P < 0.05), with the exception of increased GLUT3 messenger ribonucleic acid and protein levels in transgenic mice. The results demonstrate that triamcinolone is a potent regulator of placental GLUT1 and GLUT3 expression involving the glucocorticoid receptor. We speculate that impaired expression of placental glucose transporters after glucocorticoid administration might contribute to the adverse side-effects, the foremost of which is a growth-retarded fetus, of this treatment during pregnancy.
Hahn
T
T
Institute of Histology and Embryology, University of Graz, Austria. tom.hahn@kfunigraz.ac.at
Barth
S
S
Graf
R
R
Engelmann
M
M
Beslagic
D
D
Reul
J M
JM
Holsboer
F
F
Dohr
G
G
Desoye
G
G
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology*; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D006801:Humans; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000235:genetics*; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000502:physiology; D014327:Trophoblasts / Q000378:metabolism
D001786:Blood Glucose; D005938:Glucocorticoids; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D009004:Monosaccharide Transport Proteins; D009419:Nerve Tissue Proteins; D011965:Receptors, Glucocorticoid; C495677:SLC2A1 protein, human; C495687:SLC2A3 protein, human; C495678:Slc2a1 protein, mouse; C495679:Slc2a1 protein, rat; C495689:Slc2a3 protein, mouse; C495690:Slc2a3 protein, rat