Inhibition of cholesterylester accumulation by 17 beta-estradiol in macrophages through activation of neutral cholesterol esterase.
Premenopausal women are at a lower risk of coronary heart disease relative to age matched men. However, the underlying mechanisms are not clearly understood. This article studies the effects of 17 beta-estradiol (17 beta-E2) at physiological concentrations on the cholesterylester metabolism in macrophages (J774 A.1 cells) with a particular focus on neutral cholesterol esterase (N-CEase). Cells were incubated with beta-VLDL, [1-14C]oleic acid and 17 beta-E2 (0.25 and 2.5 nM). 17 beta-E2 dose-dependently reduced cholesteryl-[1-14C]oleate (14C-CO) at 36 h and 48 h relative to the control. It also stimulated hydrolysis of 14C-CO in foam cells on 36 h and 48 h incubation. In addition, 17 beta-E2 markedly increased N-CEase activity at 24 h and 36 h. This increase preceded the enhanced hydrolysis of cholesterylester, 17 alpha-E2 (inactive isomer), estrone and estriol had no stimulatory action on N-CEase, whereas progesterone and testosterone inhibited it. 17 beta-E2-treatment (24 h) increased the activity of cyclic AMP-dependent protein kinase (A-kinase). DEAE-cellulose column chromatography revealed that an isoform (type II) of A-kinase appeared in 17 beta-E2-treated cells in addition to type I of A-kinase found in the control cells. These results suggest that inhibition of cholesterylester accumulation in macrophages by 17 beta-E2 is mediated by an enhancement of N-CEase activity possibly through an increase in A-kinase.
Tomita
T
T
Graduate School of Health Sciences, University of Shizuoka, Japan.
Sawamura
F
F
Uetsuka
R
R
Chiba
T
T
Miura
S
S
Ikeda
M
M
Tomita
I
I
D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004789:Enzyme Activation; D004958:Estradiol / Q000494:pharmacology*; D005487:Foam Cells / Q000187:drug effects / Q000378:metabolism; D006868:Hydrolysis; D007700:Kinetics; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D051379:Mice; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology; D002787:Sterol Esterase / Q000378:metabolism*
D002788:Cholesterol Esters; D008079:Lipoproteins, VLDL; D009829:Oleic Acids; D013256:Steroids; D019301:Oleic Acid; C014409:cholesteryl oleate; D004958:Estradiol; D002784:Cholesterol; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase; D008274:Magnesium