Regulation of Cholesterol Responsive Genes in Ovary Cells:  Impact of Cholesterol Delivery Systems

The “selective” cholesterol uptake pathway represents a bulk pathway by which many steroidogenic cells internalize lipoprotein-delivered cholesteryl esters. In the current report, we question whether cholesteryl esters entering cells via this pathway are capable of governing standard cholesterol end...

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Bibliographic Details
Published in:Biochemistry (Easton) 1996-05, Vol.35 (20), p.6243-6250
Main Authors: Medicherla, Satyanarayana, Azhar, Salman, Cooper, Allen, Reaven, Eve
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Biological Transport, Active - genetics
Bucladesine - pharmacology
Cells, Cultured
Chloramphenicol O-Acetyltransferase - genetics
Chloramphenicol O-Acetyltransferase - metabolism
Cholesterol - genetics
Cholesterol - metabolism
Cholesterol Esters - metabolism
DNA Probes - genetics
Endocytosis
Feedback
Female
Gene Expression Regulation - drug effects
Granulosa Cells - metabolism
Hydroxymethylglutaryl CoA Reductases - genetics
Lipoproteins - pharmacology
Lipoproteins, HDL - metabolism
Lipoproteins, HDL3
Molecular Sequence Data
Rats
Receptors, LDL - genetics
Receptors, LDL - metabolism
RNA, Messenger - genetics
RNA, Messenger - metabolism
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Summary:The “selective” cholesterol uptake pathway represents a bulk pathway by which many steroidogenic cells internalize lipoprotein-delivered cholesteryl esters. In the current report, we question whether cholesteryl esters entering cells via this pathway are capable of governing standard cholesterol end product feedback repression mechanisms. Cultured rat ovary granulosa cells which utilize both the “selective” and “endocytic” pathways to internalize lipoprotein-derived cholesteryl esters were used as a model system. ApoE-free hHDL3 was used to deliver cholesteryl esters to the cells exclusively by the selective pathway; hLDL was used as a control ligand which when internalized by the endocytic pathway releases cholesteryl esters which subsequently regulate the expression of the B/E (LDL)-receptor, HMG CoA reductase, and acyl-CoA:cholesterol acyltransferase (ACAT). Whereas trophic hormone (Bt2cAMP) stimulation by itself increased the activity, mRNA, and protein levels of both B/E-receptor and HMG CoA reductase, pretreatment with either lipoprotein (adjusted for equal cholesterol ester content) down-regulated this expression. Linked with these lipoprotein-related changes was an increase in activity (though not gene expression) of ACAT. The level of change in mRNA levels, protein content, and activity for the examined regulatory proteins was essentially equivalent whether the lipoprotein provided to the cells was hLDL or hHDL3. Thus, similar signals appear to have been received by the cells despite differences in the uptake and processing of the ligand-derived cholesteryl esters, and these signals resulted in identical homeostatic responses by the cells.
ISSN:0006-2960
1520-4995
DOI:10.1021/bi952137l