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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1976 Dec;73(12):4329–4333. doi: 10.1073/pnas.73.12.4329

Adrenal cholesterol uptake from plasma lipoproteins: regulation by corticotropin.

J T Gwynne, D Mahaffee, H B Brewer Jr, R L Ney
PMCID: PMC431445  PMID: 188033

Abstract

The transfer of lipoprotein-bound cholesterol into adrenal cells was examined. Adrenal glands from unstimulated or corticotropin stimulated hypophysectomized rats were incubated with high density lipoprotein (HDL) or low density lipoprotein LDL containing radiolabeled cholesterol. The rate of transfer of labeled cholesterol from HDL into the glands was two to three times greater than from LDL. Corticotropin stimulation increased the transfer of cholesterol from HDL but not LDL. The effects of corticotropin were not dependent on subsequent cholesterol utilization for steroidogenesis. The process of cholesterol transfer from HDL was linear with time over 2 hr at 37 degrees and greatly reduced at 4 degrees. In addition, the transfer process became saturated above an HDL cholesterol concentration of 900 mug/ml. About 25% of the labeled adrenal cholesterol arising from HDL was recovered within the mitochondria. The labeled cholesterol within isolated mitochondria could undergo mitochondrial conversion to pregnenolone. Finally, the delipidated HDL apolipoproteins, apoA-I and apoA-II, when added to incubations containing less than saturating concentrations of HDL, stimulated transfer of labeled cholesterol from HDL to adrenal cells. These studies suggest that rat adrenal tissue possesses an HDL specific hormonally-responsive mechanism for accumulating extracellular cholesterol and that apoA-I and apoA-II have a significant function in the uptake process.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. AVIGAN J. A method for incorporating cholesterol and other lipides into serum lipoproteins in vitro. J Biol Chem. 1959 Apr;234(4):787–790. [PubMed] [Google Scholar]
  2. Anderson R. G., Goldstein J. L., Brown M. S. Localization of low density lipoprotein receptors on plasma membrane of normal human fibroblasts and their absence in cells from a familial hypercholesterolemia homozygote. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2434–2438. doi: 10.1073/pnas.73.7.2434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  4. Bierman E. L., Stein O., Stein Y. Lipoprotein uptake and metabolism by rat aortic smooth muscle cells in tissue culture. Circ Res. 1974 Jul;35(1):136–150. doi: 10.1161/01.res.35.1.136. [DOI] [PubMed] [Google Scholar]
  5. Borkowski A. J., Levin S., Delcroix C., Klastersky J. Equilibration of plasma and adrenal cholesterol in man. J Appl Physiol. 1970 Jan;28(1):42–49. doi: 10.1152/jappl.1970.28.1.42. [DOI] [PubMed] [Google Scholar]
  6. Borkowski A. J., Levin S., Delcroix C., Mahler A., Verhas V. Blood cholesterol and hydrocortisone production in man: quantitative aspects of the utilization of circulating cholesterol by the adrenals at rest and under adrenocorticotropin stimulation. J Clin Invest. 1967 May;46(5):797–811. doi: 10.1172/JCI105580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brown M. S., Goldstein J. L. Receptor-mediated control of cholesterol metabolism. Science. 1976 Jan 16;191(4223):150–154. doi: 10.1126/science.174194. [DOI] [PubMed] [Google Scholar]
  8. Dexter R. N., Fishman L. M., Ney R. L., Liddle G. W. Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies of the mechanism of action. J Clin Endocrinol Metab. 1967 Apr;27(4):473–480. doi: 10.1210/jcem-27-4-473. [DOI] [PubMed] [Google Scholar]
  9. Dexter R. N., Fishman L. M., Ney R. L. Stimulation of adrenal cholesterol uptake from plasma by adrenocorticotrophin. Endocrinology. 1970 Nov;87(5):836–846. doi: 10.1210/endo-87-5-836. [DOI] [PubMed] [Google Scholar]
  10. FARESE R. V., REDDY W. J. OBSERVATIONS ON THE INTERRELATIONS BETWEEN ADRENAL PROTEIN, RNA AND DNA DURING PROLONGED ACTH ADMINISTRATION. Biochim Biophys Acta. 1963 Sep 17;76:145–148. [PubMed] [Google Scholar]
  11. Garren L. D., Gill G. N., Masui H., Walton G. M. On the mechanism of action of ACTH. Recent Prog Horm Res. 1971;27:433–478. doi: 10.1016/b978-0-12-571127-2.50035-3. [DOI] [PubMed] [Google Scholar]
  12. Gwynne J., Brewer B., Jr, Edelhoch H. The molecular properties of ApoA-I from human high density lipoprotein. J Biol Chem. 1974 Apr 25;249(8):2411–2416. [PubMed] [Google Scholar]
  13. HAVEL R. J., EDER H. A., BRAGDON J. H. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955 Sep;34(9):1345–1353. doi: 10.1172/JCI103182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  15. Lux S. E., John K. M., Brewer H. B., Jr Isolation and characterization of apoLp-Gln-II (apoA-II), a plasma high density apolipoprotein containing two identical polypeptide chains. J Biol Chem. 1972 Dec 10;247(23):7510–7518. [PubMed] [Google Scholar]
  16. MORRIS M. D., CHAIKOFF I. L. The origin of cholesterol in liver, small intestine, adrenal gland, and testis of the rat: dietary versus endogenous contributions. J Biol Chem. 1959 May;234(5):1095–1097. [PubMed] [Google Scholar]
  17. Mahaffee D., Reitz R. C., Ney R. L. The mechanism of action of adrenocroticotropic hormone. The role of mitochondrial cholesterol accumulation in the regulation of steroidogenesis. J Biol Chem. 1974 Jan 10;249(1):227–233. [PubMed] [Google Scholar]
  18. Masket B. H., Levy R. I., Fredrickson D. S. The use of polyacrylamide gel electrophoresis in differentiating type 3 hyperlipoproteinemia. J Lab Clin Med. 1973 May;81(5):794–802. [PubMed] [Google Scholar]
  19. SPERRY W. M., WEBB M. A revision of the Schoenheimer-Sperry method for cholesterol determination. J Biol Chem. 1950 Nov;187(1):97–106. [PubMed] [Google Scholar]
  20. Schonfeld G., Felski C., Howald M. A. Characterization of the plasma lipoproteins of the genetically obese hyperlipoproteinemic Zucker fatty rat. J Lipid Res. 1974 Sep;15(5):457–464. [PubMed] [Google Scholar]
  21. Stein O., Stein Y. Comparative uptake of rat and human serum low-density and high-density lipoproteins by rat aortic smooth muscle cells in culture. Circ Res. 1975 Mar;36(3):436–443. doi: 10.1161/01.res.36.3.436. [DOI] [PubMed] [Google Scholar]
  22. Steinman R. M., Cohn Z. A. The interaction of soluble horseradish peroxidase with mouse peritoneal macrophages in vitro. J Cell Biol. 1972 Oct;55(1):186–204. doi: 10.1083/jcb.55.1.186. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. de Duve C., de Barsy T., Poole B., Trouet A., Tulkens P., Van Hoof F. Commentary. Lysosomotropic agents. Biochem Pharmacol. 1974 Sep 15;23(18):2495–2531. doi: 10.1016/0006-2952(74)90174-9. [DOI] [PubMed] [Google Scholar]

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