Abstract:
:The very low density lipoprotein/apolipoprotein-E receptor (VLDLR) is the newest member of the low density lipoprotein receptor (LDLR) family. Very little is known about VLDLR localization and regulation. Immunohistochemical analysis of human placenta with a specific polyclonal antibody detected VLDLR in syncytiotrophoblast and intermediate trophoblast 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 appearing 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 and BeWo choriocarcinoma cells, two trophoblast-derived cell lines. Treatment of these cells with 8-bromo-cAMP caused a profound suppression of VLDLR message, whereas LDLR transcripts were increased. Incubation of JEG-3 cells with 25-hydroxycholesterol did not lead to sterol negative feedback on VLDLR gene expression, unlike LDLR mRNA, which declined markedly. Insulin (200 mg/L) up-regulated VLDLR message in JEG-3 cells 2-fold, as did the fibrate hypolipidemic drug, clofibric acid. We conclude 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 trimester; and 3) the trophoblast VLDLR is subject to down-regulation by cAMP and up-regulation by insulin and fibrate hypolipidemic drugs.
journal_name
Endocrinologyjournal_title
Endocrinologyauthors
Wittmaack FM,Gåfvels ME,Bronner M,Matsuo H,McCrae KR,Tomaszewski JE,Robinson SL,Strickland DK,Strauss JF 3rddoi
10.1210/endo.136.1.7828550subject
Has Abstractpub_date
1995-01-01 00:00:00pages
340-8issue
1eissn
0013-7227issn
1945-7170journal_volume
136pub_type
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