Down-regulation of intestinal scavenger receptor class B, type I (SR-BI) expression in rodents under conditions of deficient bile delivery to the intestine

Scavenger receptor class B, type I (SR-BI) is expressed in the intestines o f rodents and has been suggested to be involved in the absorption of dietar y cholesterol. The aim of this study was to determine whether intestinal SR -BI expression is affected in animal models with altered bile delivery to t he intestine and impaired cholesterol absorption. SR-BI protein and mRNA le vels were determined in proximal and distal small intestine from control, b ile-duct-ligated and bile-diverted rats and from control and bile-duct-liga ted mice. Two genetically altered mouse models were studied: multidrug resi stance-2 P-glycoprotein-deficient [Mdr2((-/-))] mice that produce phospholi pid/cholesterol-free bile, and cholesterol 7 alpha -hydroxylase-deficient [ Cyp7a((-/-))] mice, which exhibit qualitative and quantitative changes in t he bile-salt pool. Cholesterol-absorption efficiency was quantified using a dual-isotope ratio method. SR-BI was present at the apical membrane of ent erocytes in control rats and mice and was more abundant in proximal than in distal segments of the intestine. In bile-duct-ligated animals, levels of SR-BI protein were virtually absent and mRNA levels were decreased by appro ximate to 50 %. Bile-diverted rats, Mdr2((-/-)) mice and Cyp7a((-/-)) mice showed decreased levels of intestinal SR-BI protein while mRNA levels were unaffected. Cholesterol absorption was reduced by > 90% in bile-duct-ligate d and bile-diverted animals and in Cyp7a((-/-)) mice, whereas Mdr2((-/-)) m ice showed an approximate to 50% reduction. This study shows that SR-BI is expressed at the apical membrane of enterocytes of rats and mice; mainly in the upper intestine where cholesterol absorption is greatest, and indicate s that bile components play a role in post-transcriptional regulation of SR -BI expression. Factors associated with cholestasis appear to be involved i n transcriptional control of intestinal SR-BI expression. The role of SR-BI in the cholesterol-absorption process remains to be defined.