|Title||17β-estradiol and progesterone regulate expression of β-amyloid clearance factors in primary neuron cultures and female rat brain.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Jayaraman A, Carroll JC, Morgan TE, Lin S, Zhao L, Arimoto JM, M Murphy P, Beckett TL, Finch CE, Brinton RDiaz, Pike CJ|
|Date Published||2012 Nov|
|Keywords||Amyloid beta-Peptides, Animals, Aspartic Acid Endopeptidases, Brain, Cells, Cultured, Endothelin-Converting Enzymes, Estradiol, Female, Insulysin, Metalloendopeptidases, Neprilysin, Neurons, Peptidyl-Dipeptidase A, Prealbumin, Progesterone, Rats, Rats, Sprague-Dawley|
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.
|PubMed Central ID||PMC3473201|
|Grant List||P01 AG026572 / AG / NIA NIH HHS / United States |
R01 AG034103 / AG / NIA NIH HHS / United States
AG026572 / AG / NIA NIH HHS / United States
17β-estradiol and progesterone regulate expression of β-amyloid clearance factors in primary neuron cultures and female rat brain.
Faculty Member Reference:
Roberta Diaz Brinton, Ph.D