Metabolism of low density lipoprotein by human fetal adrenal tissue

B. R. Carr, J. C. Porter, P. C. MacDonald, E. R. Simpson

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

It has been shown that lipoproteins, especiallylow density lipoproteins (LDL), support steroidogenesis in ACTH-treated human fetal adrenal tissue. To evaluate the mechanisms whereby LDL-cholesterol is used in fetal adrenal steroidogenesis, experiments were conducted to investigate the uptake and degradation of LDL. Fetal adrenal tissue obtained from human abortuses was maintained in organ culture. The tissue was incubated in the presence of lipoprotein-poor serum(LPPS) and ACTH for 3 days, and then [125I]iodo-LDL was added to the culture medium. At 37 C, the uptake of [125I]iodo- LDL commenced immediately after it was added to the medium, and maximal accumulation was attained after 4-6 h. Degradation of [125I]iodo-LDL commenced after 1 h of incubation and thereafterproceeded at a high rate in a linear fashion for at least 30 h. The relationship of the kinetics of uptake and degradation tothe concentration of [125I]iodo-LDL was indicative that these processes were ediated by binding to a common, saturable site. Further support for this interpretation was provided by thefinding that heparin, a substance which is known to displace LDL from its receptor sites, inhibited both uptake and degradation of [125I]iodo-LDL in a concentration-dependent fashion. The process of degradation was temperature sensitive, being inhibited at 4 C. In the presence of chloroquine, degradation wasinhibited completely, whereas the uptake or accumulation of [125I]iodo-LDL by the tissue was increased. Fragments of human fetal adrenal tissue were preincubated for 3 days in the presence f LPPS or LPPS plus LDL and in the presence or absence of CTH. ACTH caused a marked stimulation of [125I]iodo-LDLdegradation, but preincubation in the presence of nonradiolabeled LDL caused only a 50% decrease in [125I]iodo-LDL degradation.We conclude that LDL is taken up and degraded by human fetal adrenal tissue through a process involving bindingof LDL to specific lasma membrane receptors. After internalization of LDL, the protein component of LDL is hydrolyzed to amino acids, and the cholesterol esters are hydrolyzed to fatty acid and cholesterol. The liberated cholesterol is available for utilization in steroid biosynthesis or other cellular processes. Based on the finding that [125I]iodo-LDL degradation was reduced only partially by preincubation of fetal adrenal tissue with nonradiolabeled LDL together with the finding that ACTH caused a striking increase in LDL degradation, we conclude that he fetal adrenal is refractory to down-regulation of its LDL eceptors by LDL, and that the most important factor regulating LDL metabolism is ACTH.

Original languageEnglish (US)
Pages (from-to)1034-1040
Number of pages7
JournalEndocrinology
Volume107
Issue number4
DOIs
StatePublished - Oct 1980

ASJC Scopus subject areas

  • Endocrinology

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