17 beta-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 alt ernatively spliced product of the SR-BI gene that only differs in the C-ter minal cytoplasmic domain. Previous studies with male mice demonstrated that SR-BII comprises about 12% of the total SR-BI/SR-BII present in Ever. In t he current studies we used a liver cell line, HepG2, and a rat estrogen rep lacement model to examine the effects of estrogen on the expression of SR-B H. HepG2 cells express SR-BI but not SR-BII. SR-BI/SR-BII-blocking antibodi es demonstrated that HepG2 cells selectively internalize cholesterol esters in a SR-BI-dependent manner. Incubation of HepG2 cells with 10 pM of 17 be ta -estradiol for 12 h eliminated the expression of SR-BI and promoted the up-regulation of SR-BII. Radiolabeled HDL-binding studies demonstrated that 17 beta -estradiol increased the number of HDL binding sites by 3-fold in HepG2 cells. However, 17 beta -estradiol-treated cell internalized approxim ately 25% less cholesterol ester than vehicle-only-treated cells. The liver s obtained from male rats and ovariectomized female rats contained SR-BI an d a small amount of SR-BU. In contrast, the livers obtained from intact fem ale rats and ovariectomized female rats receiving estrogen replacement cont ained 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-BH in HepG2 cells and rat liver.