Developmental expression of Glut1 glucose transporter and c-fos genes in human placental cells

Glut1, the brain/erythrocyte glucose transporter is one major isoform of the human placenta and displays an age-specific pattern of expression with mRNA levels five-fold higher in first trimester than in term placenta. By contrast, the mRNA level of the insulin-regulatable glucose transporter Glut4 remains at the limit of detection throughout pregnancy indicating a very low expression of this isoform in the placenta. The nuclear proto-oncogenes c-fos and c-myc were also detectable in the human placenta, but c-fos only exhibited an age-specific pattern of expression with levels higher in third trimester than in term placenta. Primary cultures of human trophoblast cells from term placenta were used to further study the expression and regulation of Glut1 and c-fos genes. Fetal calf serum rapidly and transiently (15 to 60 min) stimulated c-fos and Glut1 gene expression suggesting that both genes share similar growth factor-controlled pathways. Glucose inhibited Glut1, but not c-fos expression. An eight-fold decrease in Glut1 mRNA was observed when glucose concentration in the medium was increased from 0 to 25 mM, whereas c-fos mRNA levels remained very low. These results suggest that in the human placenta, the expression of Glut1 is specifically regulated by glucose concentration. These data demonstrate that (1) Glut1 and c-fos mRNA transcripts are expressed in the human placenta exhibiting an age-specific pattern of expression, (2) In cultured trophoblast cells, both genes are stimulatable by fetal calf serum and in contrast to c-fos, Glut1 is negatively regulated by glucose. This differential regulation of Glut1 and c-fos genes could be relevant to specific metabolic and mitogenic pathways implicated in placental growth and differentiation.