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Correspondence to:
Eric J. Smart, To whom correspondence should be addressed., ejsmart{at}pop.uky.edu (E-mail)
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 17ß-estradiol for 12 h eliminated the expression of SR-BI and promoted the up-regulation of SR-BII. Radiolabeled HDL-binding studies demonstrated that 17ß-estradiol increased the number of HDL binding sites by 3-fold in HepG2 cells. However, 17ß-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., K. L. Roswell, and E. J. Smart. 17ß-Estradiol promotes the up-regulation of SR-BII in HepG2 cells and in rat livers. J. Lipid Res. 2001. 42: 1444;–1449.
Supplementary key words:
HDL, cholesterol ester, scavenger receptor, selective uptake
Copyright © 2001 by Lipid Research, Inc.
Original Article
17ß-Estradiol promotes the up-regulation of SR-BII in HepG2 cells and in rat livers
Gregory A. Grafa,
Kathy L. Roswella, and
Eric J. Smarta
a University of Kentucky Medical School, Department of Physiology, Lexington, KY 40536
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