The LDL receptor is not necessary for acute adrenal steroidogenesis in mouse adrenocortical cells.
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.
Kraemer
Fredric B
FB
Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA. fbk@stanford.edu
Shen
Wen-Jun
WJ
Patel
Shailja
S
Osuga
Jun-Ichi
J
Ishibashi
Shun
S
Azhar
Salman
S
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
D002788:Cholesterol Esters; D011973:Receptors, LDL; D013256:Steroids; D002787:Sterol Esterase; D003345:Corticosterone