Uptake and utilization of lipoprotein cholesteryl esters by rat granulosa cells.
Earlier studies have shown that rat granulosa cells grown in serum-free medium are exquisitely responsive to exogenously provided lipoprotein cholesterol. In this study we compare the amount of cholesterol (cholesteryl ester) actually delivered from various homologous and heterologous cholesterol-rich lipoproteins and examine the intracellular pathways used in the delivery system. Granulosa cells were incubated for 5 or 24 h with 125I-labeled human (h) HDL3, rat (r) HDL or hLDL equipped with non-releasable apoprotein and cholesteryl ether tags which accumulate within cells, even after degradation. We show that all the tested lipoproteins were similarly efficient in cholesteryl ester delivery; i.e., based on cholesterol: protein ratios of the starting ligands, each delivered approximately the same cholesteryl ester mass and evoked a similar progestin response. However, each lipoprotein was processed quite differently by the granulosa cells: hHDL3-cholesteryl ester was taken up almost exclusively by an non-endocytic pathway, hLDL-cholesteryl ester almost exclusively by an endocytic pathway and rHDL-cholesteryl ester by both pathways. In general, there was no correlation between the total amount of lipoprotein bound or apoprotein internalized and/or degraded by the cells with the amount of cholesteryl ester received or the level of the progestin response. Hormone stimulation upregulated the preferred pathway for each lipoprotein.
Azhar
S
S
Department of Medicine, Stanford University School of Medicine, CA.
Tsai
L
L
Reaven
E
E
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism*; D004705:Endocytosis; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D007457:Iodine Radioisotopes; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL / Q000378:metabolism; D008854:Microscopy, Electron; D051381:Rats; D011919:Rats, Inbred Strains; D014439:Tyramine / Q000031:analogs & derivatives
D002788:Cholesterol Esters; D007457:Iodine Radioisotopes; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D053440:Lipoproteins, HDL3; D008077:Lipoproteins, LDL; D003994:Bucladesine; C027575:cholesteryl linoleyl ether; D002784:Cholesterol; C049133:dilactitol tyramine; D014439:Tyramine