Hormonal modulators of glial ABCA1 and apoE levels[S]

Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provid...

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Bibliographic Details
Published in:	Journal of lipid research Vol. 54; no. 11; pp. 3139 - 3150
Main Authors:	Fan, Jianjia, Shimizu, Yoko, Chan, Jeniffer, Wilkinson, Anna, Ito, Ayaka, Tontonoz, Peter, Dullaghan, Edie, Galea, LiisaA.M., Pfeifer, Tom, Wellington, Cheryl L.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-11-2013 The American Society for Biochemistry and Molecular Biology Elsevier
Subjects:	Animals Apolipoprotein A-I - metabolism apolipoprotein E Apolipoprotein E3 - metabolism Apolipoproteins E - genetics Apolipoproteins E - metabolism Astrocytes - drug effects Astrocytes - metabolism astrocytoma ATP Binding Cassette Transporter 1 - genetics ATP Binding Cassette Transporter 1 - metabolism ATP binding cassette transporter A1 Biological Transport - drug effects Cell Line Cholesterol - metabolism Estrogens - pharmacology Homeostasis - drug effects Hormones - pharmacology Humans liver X receptor Liver X Receptors Lynestrenol - pharmacology Mice Neuroglia - drug effects Neuroglia - metabolism Orphan Nuclear Receptors - metabolism progesterone Progesterone - pharmacology progestin Receptors, Progesterone - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Sterol Regulatory Element Binding Protein 1 - genetics Up-Regulation - drug effects apolipoprotein E ATP binding cassette transporter A1 progestin astrocytoma liver X receptor progesterone
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Summary:	Apolipoprotein E (apoE) is the major lipid carrier in the central nervous system. As apoE plays a major role in the pathogenesis of Alzheimer disease (AD) and also mediates repair pathways after several forms of acute brain injury, modulating the expression, secretion, or function of apoE may provide potential therapeutic approaches for several neurological disorders. Here we show that progesterone and a synthetic progestin, lynestrenol, significantly induce apoE secretion from human CCF-STTG1 astrocytoma cells, whereas estrogens and the progesterone metabolite allopregnanolone have negligible effects. Intriguingly, lynestrenol also increases expression of the cholesterol transporter ABCA1 in CCF-STTG1 astrocytoma cells, primary murine glia, and immortalized murine astrocytes that express human apoE3. The progesterone receptor inhibitor RU486 attenuates the effect of progestins on apoE expression in CCF-STTG1 astrocytoma cells but has no effect on ABCA1 expression in all glial cell models tested, suggesting that the progesterone receptor (PR) may participate in apoE but does not affect ABCA1 regulation.These results suggest that selective reproductive steroid hormones have the potential to influence glial lipid homeostasis through liver X receptor-dependent and progesterone receptor-dependent pathways.
ISSN:	0022-2275 1539-7262
DOI:	10.1194/jlr.M042473