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Role of high-density lipoproteins and apolipoprotein A-I in steroid hormone synthesis

The mechanism of cellular uptake of cholesterol, which is a "hot issue" in lipidology and atherosclerosis research, is also important for the understanding of steroidogenesis. Indeed, the availability of cholesterol for steroid hormone production in adrenal cortical cells is thought to depend more on cholesterol import rather than on synthesis. In the circulation, cholesterol is associated with lipoprotein particles, mostly with low-density lipoproteins (LDLs) and high-density lipoproteins (HDLs).

Brown and Goldstein elegantly demonstrated that the uptake of cholesterol from LDL particles involves receptor-mediated uptake of whole particles and their degradation in an endolysosomal compartment (1). In contrast, the uptake of cholesterol from HDL particles is much less well understood. High-density lipoproteins are believed to be responsible for transferring cholesterol from peripheral tissues to the liver, where it is taken up by hepatocytes for degradation (the so-called "reverse cholesterol transport"). The HDL particles contain a core of cholesteryl ester (CE) surrounded