HDL biology
CETP-mediated cholesterol transfer cannot substitute for SR-BI in adrenal steroid production (J Lipid Res 2009)
Original title: Scavenger receptor class B type I-mediated uptake of serum cholesterol is essential for optimal adrenal glucocorticoid production
Testing whether CETP-mediated transfer of HDL-cholesteryl esters to apoB lipoproteins can compensate for loss of adrenal SR-BI, transgenic human CETP expression in SR-BI knockout mice increased adrenal HDL-cholesteryl-ester clearance from 33-58% of the control value. Yet SR-BI knockout mice with and without CETP expression both showed adrenal hypertrophy from equally elevated ACTH, and adrenal cholesterol and plasma corticosterone were 38-52% decreased regardless of CETP status. SR-BI-KO/CETP-Tg mice also failed to raise corticosterone after a lipopolysaccharide challenge, showing an identical greater than 4-fold increase in tumor necrosis factor-alpha versus controls. CETP-mediated HDL-cholesteryl-ester transfer therefore cannot reverse the adrenal insufficiency caused by SR-BI loss.
Original abstract
Impaired scavenger receptor class B type I (SR-BI)-mediated uptake of HDL-cholesterol esters (HDL-CE) induces adrenal insufficiency in mice. Humans contain an alternative route of HDL-CE clearance, namely through the transfer by cholesteryl ester transfer protein (CETP) to apolipoprotein B lipoproteins for subsequent uptake via the LDL receptor. In this study, we determined whether CETP can compensate for loss of adrenal SR-BI. Transgenic expression of human CETP (CETP Tg) in SR-BI knockout (KO) mice increased adrenal HDL-CE clearance from 33-58% of the control value. SR-BI KO/CETP Tg and SR-BI KO mice displayed adrenal hypertrophy due to equally high plasma adrenocorticotropic hormone levels. Adrenal cholesterol levels and plasma corticosterone levels were 38-52% decreased in SR-BI KO mice with and without CETP expression. SR-BI KO/CETP Tg mice also failed to increase their corticosterone level after lipopolysaccharide challenge, leading to an identical >4-fold increased tumor necrosis factor-alpha response compared with controls. These data indicate that uptake of CE via other routes than SR-BI is not sufficient to generate the cholesterol pool needed for optimal adrenal steroidogenesis. In conclusion, we have shown that CETP-mediated transfer of HDL-CE is not able to reverse adrenal insufficiency in SR-BI knockout mice. Thus, SR-BI-mediated uptake of serum cholesterol is essential for optimal adrenal function.
HDL biologyinfectionmechanisms
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.