LOCALIZATION AND REGULATION OF THE HUMAN VERY-LOW-DENSITY LIPOPROTEINAPOLIPOPROTEIN-E RECEPTOR - TROPHOBLAST EXPRESSION PREDICTS A ROLE FOR THE RECEPTOR IN PLACENTAL LIPID TRANSPORT

The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest member of the low density lipoprotein receptor (LDLR) famil y. Very little is known about VLDLR localization and regulation. Immun ohistochemical analysis of human placenta with a specific polyclonal a ntibody detected VLDLR in syncytiotrophoblast and intermediate trophob last cells. VLDLR transcripts were also localized in these cells by in situ hybridization histochemistry. In addition, VLDLR messenger RNA ( mRNA) was detected in villous core endothelial cells and cells appeari ng to be Hofbauer cells. Northern blot analysis of placenta revealed a 2.6-fold increase in VLDLR mRNA at term compared to that in the first trimester. The regulation of VLDLR expression was studied in JEG-3 an d BeWo choriocarcinoma cells, two trophoblast-derived cell lines. Trea tment of these cells with 8-bromo-cAMP caused a profound suppression o f VLDLR message, whereas LDLR transcripts were increased. Incubation o f JEG-3 cells with 25-hydroxycholesterol did not lead to sterol negati ve feedback on VLDLR gene expression, unlike LDLR mRNA, which declined markedly. Insulin (200 mg/L) up-regulated VLDLR message in JEG-3 cell s 2-fold, as did the fibrate hypolipidemic drug, clofibric acid. We co nclude that 1) VLDLR is expressed in human placental trophoblast cells in a pattern consistent with a role in placental lipid transport; 2) VLDLR expression is high at term relative to that in the first trimest er; and 3) the trophoblast VLDLR is subject to down-regulation by cAMP and up-regulation by insulin and fibrate hypolipidemic drugs.