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This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/E408    most recent 00428.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Kraemer, F. B. Articles by Azhar, S. Search for Related Content PubMed PubMed Citation Articles by Kraemer, F. B. Articles by Azhar, S.

The LDL receptor is not necessary for acute adrenal steroidogenesis in mouse adrenocortical cells

¹Veterans Affairs Palo Alto Health Care System, Palo Alto; ²Department of Medicine, Stanford University, Stanford, California; ³Department of Metabolic Disease, University of Tokyo, Tokyo; and ⁴Department of Internal Medicine, Jichi Medical School, Tochigi, Japan

Submitted 18 August 2006 ; accepted in final form 16 September 2006

Steroid hormones are synthesized using cholesterol as precursor. To determine the functional importance of the low density lipoprotein (LDL) receptor and hormone-sensitive lipase (HSL) in adrenal steroidogenesis, adrenal cells were isolated from control, HSL^–/–, LDLR^–/–, and double LDLR/HSL^–/– mice. The endocytic and selective uptake of apolipoprotein E-free human high density lipoprotein (HDL)-derived cholesteryl esters did not differ among the mice, with selective uptake accounting for >97% of uptake. In contrast, endocytic uptake of either human LDL- or rat HDL-derived cholesteryl esters was reduced 80–85% in LDLR^–/– and double-LDLR/HSL^–/– mice. There were no differences in the selective uptake of either human LDL- or rat HDL-derived cholesteryl esters among the mice. Maximum corticosterone production induced by ACTH or dibutyryl cyclic AMP and lipoproteins was not altered in LDLR^–/– mice but was reduced 80–90% in HSL^–/– mice. Maximum corticosterone production was identical in HSL^–/– and double-LDLR/HSL^–/– mice. These findings suggest that, although the LDL receptor is responsible for endocytic delivery of cholesteryl esters from LDL and rat HDL to mouse adrenal cells, it appears to play a negligible role in the delivery of cholesterol for acute adrenal steroidogenesis in the mouse. In contrast, HSL occupies a vital role in adrenal steroidogenesis because of its link to utilization of selectively delivered cholesteryl esters from lipoproteins.

neutral cholesteryl ester hydrolase; corticosterone; cholesterol; receptor low density lipoprotein; selective pathway; hormone-sensitive lipase