Expression of the human apolipoprotein E gene suppresses steroidogenesis in mouse Y1 adrenal cells.
The lipid transport protein, apolipoprotein E (apoE), is expressed in many peripheral tissues in vivo including the adrenal gland and testes. To investigate the role of apoE in adrenal cholesterol homeostasis, we have expressed a human apoE genomic clone in the Y1 mouse adrenocortical cell line. Y1 cells do not express endogenous apoE mRNA or protein. Expression of apoE in Y1 cells resulted in a dramatic decrease in basal steroidogenesis; secretion of fluorogenic steroid was reduced 7- to greater than 100-fold relative to Y1 parent cells. Addition of 5-cholesten-3 beta,25-diol failed to overcome the suppression of steroidogenesis in these cells. Cholesterol esterification under basal conditions, as measured by the production of cholesteryl [14C]oleate, was similar in the Y1 parent and the apoE-transfected cell lines. Upon incubation with adrenocorticotropin or dibutyryl cAMP, production of cholesteryl [14C]oleate decreased 5-fold in the Y1 parent cells but was unchanged in the apoE-transfected cell lines. These results suggest that apoE may be an important modulator of cholesterol utilization and steroidogenesis in adrenal cells.
Reyland
M E
ME
Department of Pharmacological Sciences, State University of New York, Stony Brook 11794.
Gwynne
J T
JT
Forgez
P
P
Prack
M M
MM
Williams
D L
DL
D000311:Adrenal Glands; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D015152:Blotting, Northern; D003994:Bucladesine / Q000494:pharmacology; D002460:Cell Line; D002788:Cholesterol Esters / Q000096:biosynthesis*; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007700:Kinetics; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013256:Steroids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014162:Transfection
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D012333:RNA, Messenger; D013256:Steroids; C014409:cholesteryl oleate; D003994:Bucladesine; D000324:Adrenocorticotropic Hormone