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Rat granulosa cell apolipoprotein E secretion. Regulation by cell cholesterol
K L Wyne1, J R Schreiber, A L Larsen
1Department of Pathology, University of Chicago, Illinois 60637.
The Journal of Biological Chemistry
|October 5, 1989
Summary
Cholesterol synthesis products are essential for regulating apolipoprotein E (apoE) production in rat ovarian granulosa cells. Inhibiting cholesterol synthesis reduces apoE, but this effect is reversed by adding back key cholesterol precursors.
Area of Science:
- Reproductive biology
- Molecular endocrinology
- Lipid metabolism
Background:
- Rat ovarian granulosa cells synthesize and secrete apolipoprotein E (apoE).
- apoE production is stimulated by agents activating protein kinase A and protein kinase C.
Purpose of the Study:
- To investigate the impact of altered cholesterol synthesis on apoE production in rat ovarian granulosa cells.
Main Methods:
- Utilized mevinolin (HMG-CoA reductase inhibitor) and a squalene cyclization inhibitor.
- Administered mevalolactone to reverse mevinolin's effects.
- Assessed apoE secretion and apoE mRNA levels.
- Examined the effect of aminoglutethimide on steroidogenesis.
Main Results:
- Inhibitors of cholesterol synthesis dose-dependently reduced apoE secretion and apoE mRNA stimulated by cholera toxin or phorbol ester.
- Mevinolin's inhibitory effect was reversed by mevalolactone.
- Steroidogenesis, even when inhibited, did not affect apoE production.
Conclusions:
- Products of HMG-CoA reductase, including isoprenes and cholesterol, are necessary for regulating apoE production.
- Regulation of ovarian granulosa cell apoE production requires both protein kinase activators and HMG-CoA reductase products.