Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores. In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control.
Scavenger receptor BI (SR-BI), a putative high density lipoprotein (HDL) receptor, mediates the selective uptake of HDL cholesteryl ester into cells and is highly expressed in adrenal gland (Acton, S., Rigotti, A., Landschulz, K.T., Xu, S., Hobbs, H.H., and Krieger, M. (1996) Science 271, 518-520). Apolipoprotein A-I knock-out (apoA-I0) mice have decreased HDL cholesterol, depleted adrenal cholesterol stores and impaired corticosteroid synthesis (Plump, A.S., Erickson, S.K., Weng, W., J. Clin. Invest. 97, 2660-2671). We now show up-regulation of adrenal SR-BI mRNA and protein in apoA-I0 mice, but not in apoA-II0, LDL receptor 0, apoE0, or cholesteryl ester transfer protein transgenic mice. Adrenal SR-BI mRNA and protein are also increased and cholesterol stores decreased in female mice with knockout of hepatic lipase, and enzyme previously shown to increase selective uptake in cell culture. SR-BI mRNA is increased in stressed wild type mice and in Y1 adrenal cells treated with adrenocorticotropic hormone; the latter effect is inhibited by HDL. These findings provide in vivo evidence showing SR-BI is a functional HDL receptor under feedback control. The action of hepatic lipase on apoA-I-containing lipoproteins may facilitate the SR-BI-mediated uptake of HDL lipid.
Wang
N
N
Department of Medicine, Columbia University, New York, New York 10032, USA.
Weng
W
W
Breslow
J L
JL
Tall
A R
AR
D000311:Adrenal Glands / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics*; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins; D002784:Cholesterol / Q000378:metabolism*; D005246:Feedback; D005260:Female; D008049:Lipase / Q000235:genetics*; D008075:Lipoproteins, HDL; D008099:Liver / Q000201:enzymology; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein / Q000378:metabolism; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D015854:Up-Regulation
D016632:Apolipoprotein A-I; D018955:CD36 Antigens; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C031616:high density lipoprotein receptors; C075197:high density lipoprotein binding protein; D002784:Cholesterol; D008049:Lipase