Receptor mediated uptake of low density lipoprotein and utilization of its cholesterol for steroid synthesis in cultured mouse adrenal cells

Research output: Contribution to journalArticle

182 Scopus citations

Abstract

Steroid-secreting cultured mouse adrenal cells of the Y-1 clone were shown to possess a high affinity cell surface receptor for plasma low density lipoprotein (LDL). Binding of either human or mouse LDL to the receptor was followed by the uptake of the lipoprotein and the hydrolysis of its protein and cholesteryl ester components within lysosomes. In the absence of adrenocorticotropin (ACTH), the LDL-derived cholesterol suppressed the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, enhanced the rate of incorporation of [14C] oleate into cholesteryl esters, and suppressed the activity of the LDL receptor. In the presence of ACTH, the LDL-derived cholesterol was converted to 21-carbon steroids (chiefly, 11-β-hydroxy-20-α-dihydroprogesterone). When the mouse adrenal cells were grown in the presence of ACTH but in the absence of lipoproteins, the availability of cholesterol became rate-limiting for steroid synthesis. The subsequent addition of LDL to the culture medium caused a large intracellular accumulation of cholesteryl esters and enhanced the rate of steroid secretion by 4-fold. Under these conditions, more than 75% of the secreted steroid was derived from LDL that entered cells through the receptor-mediated pathway. When the rate of steroid secretion was high, the amount of cholesterol that could be derived from LDL was not sufficient to suppress completely the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase or to stimulate fully the incorporation of [14C] oleate into cholesteryl esters. High density lipoprotein (HDL) derived from either human or mouse plasma did not bind to the LDL receptor on mouse adrenal cells as indicated by its inability to compete effectively with 125I-LDL for binding and degradation. As a result, HDL did not increase the cholesterol content of the adrenal cells nor was it able to suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase or provide cholesterol substrate for steroid synthesis.

Original languageEnglish (US)
Pages (from-to)4861-4871
Number of pages11
JournalJournal of Biological Chemistry
Volume252
Issue number14
StatePublished - Dec 1 1977

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this