title: The LDL receptor is not necessary for acute adrenal steroidogenesis in mouse adrenocortical cells.
abstract: 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.
authors.affiliation: Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. fbk@stanford.edu
authors.forename: Fredric B
authors.initials: FB
authors.lastname: Kraemer
authors.forename: Wen-Jun
authors.initials: WJ
authors.lastname: Shen
authors.forename: Shailja
authors.initials: S
authors.lastname: Patel
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Salman
authors.initials: S
authors.lastname: Azhar
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D002788:Cholesterol Esters / Q000378:metabolism; D003345:Corticosterone / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D013256:Steroids / Q000096:biosynthesis*; D002787:Sterol Esterase / Q000235:genetics / Q000502:physiology
chemical_list: D002788:Cholesterol Esters; D011973:Receptors, LDL; D013256:Steroids; D002787:Sterol Esterase; D003345:Corticosterone