Testosterone up-regulates scavenger receptor BI and stimulates cholesterol efflux from macrophages.
By lowering high density lipoprotein (HDL) cholesterol, testosterone contributes to the gender difference in HDL cholesterol and has been accused to be pro-atherogenic. The mechanism by which testosterone influences HDL cholesterol is little understood. We therefore investigated the effect of testosterone on the gene expression of apolipoprotein A-I (apoA-I), hepatic lipase (HL), scavenger receptor B1 (SR-BI), and the ATP binding cassette transporter A1 (ABCA1), all of which are important regulators of HDL metabolism. In both cultivated HepG2 hepatocytes and primary human monocyte-derived macrophages, testosterone led to a dose-dependent up-regulation of SR-BI, which was assessed on both the mRNA and the protein levels. As a functional consequence, we observed an increased HDL(3)-induced cholesterol efflux from macrophages. At supraphysiological dosages, testosterone also increased the expression of HL in HepG2 cells. Testosterone had no effect on the expression of apoA-I in HepG2 cells and ABCA1 in either HepG2 cells or macrophages. These data suggest that testosterone, despite lowering HDL cholesterol, intensifies reverse cholesterol transport and thereby exerts an anti-atherogenic rather than a pro-atherogenic effect.
Institut für Arterioskleroseforschung an der Universität Münster, Domagkstrasse 3, D-48149, Münster, Germany.
Claus
C
Langer
Barbara
B
Gansz
Christian
C
Goepfert
Thomas
T
Engel
Yoshinari
Y
Uehara
Gerlinde
G
von Dehn
Hans
H
Jansen
Gerd
G
Assmann
Arnold
A
von Eckardstein
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics; D016632:Apolipoprotein A-I / Q000096:biosynthesis / Q000235:genetics; D001692:Biological Transport; D018955:CD36 Antigens / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008049:Lipase / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013739:Testosterone / Q000494:pharmacology*; D015854:Up-Regulation
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D016632:Apolipoprotein A-I; D018955:CD36 Antigens; D008565:Membrane Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D013739:Testosterone; D002784:Cholesterol; D008049:Lipase