Direct Evidence for Sterol Carrier Protein-2 (SCP-2) Participation in ACTH Stimulated Steroidogenesis in Isolated Adrenal Cells
Intact, dispersed adrenal fasiculata cells were fused with liposomal entrapped anti-sterol carrier protein-2 IgG, washed and subsequently exposed to adrenocorticotropic hormone (ACTH). The steroidogenic response (measured as corticosterone production) of these cells was inhibited by 45–60%, compared to cells fused with liposomally entrapped non-immune IgG or buffer. Furthermore, the degree of inhibition was shown to be dependent on the amount of antibody utilized. Fusion of cells with liposomally entrapped antibody to fatty acid binding protein (FABP) had no effect on ACTH-induced steroidogenesis. The incorporation of liposomal SCP-2 into adrenal fasiculata cells pre-treated with affinity purified anti-SCP-2 IgG resulted in a concentration dependent release of the inhibition of ACTH-induced steroidogenesis caused by the antibody. It was also demonstrated indirectly that the fusion of liposomal anti-SCP-2 IgG had no effect on ACTH binding to adrenal cells. Finally, cells treated with liposomal anti-SCP-2 IgG and subsequently exposed to ACTH in the presence of aminoglutethimide, accumulated unesterified cholesterol in their cytoplasmic lipid inclusion droplets. These results, taken together, establish that an important physiological function for SCP-2 in adrenal cells is the transfer of unesterified cholesterol from the cytoplasmic lipid inclusion droplets to mitochondria. This translocation is generally considered to be the rate-limiting step in steroid hormone biosynthesis.
Key Wordssterol carrier protein-2 (SCP-2) intracellular cholesterol transport regulation of steroidogenesis
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