title: 17β-estradiol and progesterone regulate expression of β-amyloid clearance factors in primary neuron cultures and female rat brain.
abstract: The accumulation of β-amyloid protein (Aβ) is a key risk factor in the development of Alzheimer's disease. The ovarian sex steroid hormones 17β-estradiol (E(2)) and progesterone (P(4)) have been shown to regulate Aβ accumulation, although the underlying mechanism(s) remain to be fully elucidated. In this study, we investigate the effects of E(2) and P(4) treatment on the expression levels of Aβ clearance factors including insulin-degrading enzyme, neprilysin, endothelin-converting enzyme 1 and 2, angiotensin-converting enzyme, and transthyretin, both in primary neuron cultures and female rat brains. Our results show that E(2) and P(4) affect the expression levels of several Aβ clearance factors in dose- and time-dependent manners. Most notably, expression of insulin-degrading enzyme is significantly increased by both hormones in cultured neurons and in vivo and is inversely associated with the soluble Aβ levels in vivo. These findings further define sex steroid hormone actions involved in regulation of Aβ, a relationship potentially important to therapeutic approaches aimed at reducing risk of Alzheimer's disease.
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Anusha
authors.initials: A
authors.lastname: Jayaraman
authors.forename: Jenna C
authors.initials: JC
authors.lastname: Carroll
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.forename: Sharon
authors.initials: S
authors.lastname: Lin
authors.forename: Liqin
authors.initials: L
authors.lastname: Zhao
authors.forename: Jason M
authors.initials: JM
authors.lastname: Arimoto
authors.forename: M Paul
authors.initials: MP
authors.lastname: Murphy
authors.forename: Tina L
authors.initials: TL
authors.lastname: Beckett
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.forename: Roberta Diaz
authors.initials: RD
authors.lastname: Brinton
authors.forename: Christian J
authors.initials: CJ
authors.lastname: Pike
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D000072396:Endothelin-Converting Enzymes; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007339:Insulysin / Q000235:genetics / Q000378:metabolism; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D015260:Neprilysin / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D011228:Prealbumin / Q000235:genetics / Q000378:metabolism; D011374:Progesterone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016229:Amyloid beta-Peptides; D011228:Prealbumin; D011374:Progesterone; D004958:Estradiol; D007703:Peptidyl-Dipeptidase A; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D015260:Neprilysin; D007339:Insulysin; D000072396:Endothelin-Converting Enzymes