17beta-Estradiol promotes the up-regulation of SR-BII in HepG2 cells and in rat livers.
The scavenger receptor class B type I (SR-BI) binds to HDL and mediates the selective uptake of cholesterol esters from HDL to cells. SR-BII is an alternatively spliced product of the SR-BI gene that only differs in the C-terminal cytoplasmic domain. Previous studies with male mice demonstrated that SR-BII comprises about 12% of the total SR-BI/SR-BII present in liver. In the current studies we used a liver cell line, HepG2, and a rat estrogen replacement model to examine the effects of estrogen on the expression of SR-BII. HepG2 cells express SR-BI but not SR-BII. SR-BI/SR-BII - blocking antibodies demonstrated that HepG2 cells selectively internalize cholesterol esters in a SR-BI - dependent manner. Incubation of HepG2 cells with 10 pM of 17beta-estradiol for 12 h eliminated the expression of SR-BI and promoted the up-regulation of SR-BII. Radiolabeled HDL-binding studies demonstrated that 17beta-estradiol increased the number of HDL binding sites by 3-fold in HepG2 cells. However, 17beta-estradiol - treated cell internalized approximately 25% less cholesterol ester than vehicle-only-treated cells. The livers obtained from male rats and ovariectomized female rats contained SR-BI and a small amount of SR-BII. In contrast, the livers obtained from intact female rats and ovariectomized female rats receiving estrogen replacement contained SR-BII and a small amount of SR-BI. The amount of SR-BI and SR-BII in adrenal tissue was not affected by any of the experimental treatments. We conclude that estrogen up-regulates SR-BII in HepG2 cells and rat liver.
Graf
G A
GA
University of Kentucky Medical School, Department of Physiology, Lexington, KY 40536, USA.
Roswell
K L
KL
Smart
E J
EJ
D017398:Alternative Splicing; D000818:Animals; D018955:CD36 Antigens / Q000032:analysis / Q000235:genetics*; D016466:CHO Cells; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D006224:Cricetinae; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D014162:Transfection; D014407:Tumor Cells, Cultured
D018955:CD36 Antigens; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D004958:Estradiol