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 HDL3-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.

ABCA1, Androgens, HDL, Hepatic lipase, Reverse cholesterol transport, Scavenger receptor, Sex hormones
dx.doi.org/10.1016/S0006-291X(02)02038-7, hdl.handle.net/1765/61551
Biochemical and Biophysical Research Communications
Department of Internal Medicine

Langer, C, Gansz, B, Goepfert, C, Engel, T, Uehara, Y, von Dehn, G, … von Eckardstein, A. (2002). Testosterone up-regulates scavenger receptor bi and stimulates cholesterol efflux from macrophages. Biochemical and Biophysical Research Communications, 296(5), 1051–1057. doi:10.1016/S0006-291X(02)02038-7