title: Hormonal modulators of glial ABCA1 and apoE levels.
abstract: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine University of British Columbia, Vancouver, BC, Canada.
authors.forename: Jianjia
authors.initials: J
authors.lastname: Fan
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Jeniffer
authors.initials: J
authors.lastname: Chan
authors.forename: Anna
authors.initials: A
authors.lastname: Wilkinson
authors.forename: Ayaka
authors.initials: A
authors.lastname: Ito
authors.forename: Peter
authors.initials: P
authors.lastname: Tontonoz
authors.forename: Edie
authors.initials: E
authors.lastname: Dullaghan
authors.forename: Liisa A M
authors.initials: LA
authors.lastname: Galea
authors.forename: Tom
authors.initials: T
authors.lastname: Pfeifer
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Wellington
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000378:metabolism; D053318:Apolipoprotein E3 / Q000378:metabolism; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D004967:Estrogens / Q000494:pharmacology; D006706:Homeostasis / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology*; D006801:Humans; D000071518:Liver X Receptors; D008234:Lynestrenol / Q000494:pharmacology; D051379:Mice; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism*; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D004967:Estrogens; D006728:Hormones; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D051780:Sterol Regulatory Element Binding Protein 1; D011374:Progesterone; D002784:Cholesterol; D008234:Lynestrenol
keywords: ATP binding cassette transporter A1; apolipoprotein E; astrocytoma; liver X receptor; progesterone; progestin