Testosterone stimulates rapid secretory amyloid precursor protein release from rat hypothalamic cells via the activation of the mitogen-activated protein kinase pathway

The processing of the amyloid precursor protein (APP) has become a major focus of research into Alzheimer's disease (AD). Recently, repeated doses of testosterone have been shown to enhance the secretion of the product of the α-cleavage pathway of APP (sAPPα) over a period of days. Here, the ti...

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Bibliographic Details
Published in:Neuroscience letters 2000-12, Vol.296 (1), p.49-52
Main Authors: Goodenough, Sharon, Engert, Stefanie, Behl, Christian
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amyloid beta-Protein Precursor - metabolism
Amyloid precursor protein
Animals
Biological and medical sciences
Cell Line
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Hypothalamus - drug effects
Hypothalamus - metabolism
Kinetics
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Medical sciences
Mitogen-activated protein kinase
Mitogen-Activated Protein Kinase 1 - metabolism
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases - metabolism
Neurology
Neurons - drug effects
Neurons - metabolism
Phosphorylation
Rats
Testosterone
Testosterone - pharmacology
Testosterone - physiology
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Summary:The processing of the amyloid precursor protein (APP) has become a major focus of research into Alzheimer's disease (AD). Recently, repeated doses of testosterone have been shown to enhance the secretion of the product of the α-cleavage pathway of APP (sAPPα) over a period of days. Here, the time course of secretion of sAPPα after a single physiological dose of testosterone using an immortalized rat hypothalamic cell line (GT1–7) and the signalling pathways involved was analyzed. Testosterone was found to increase the amount of APP secretion rapidly after treatment without effecting the overall amount of cellular APP. The species of APP secreted was found to be predominantly the product of the non-amyloidogenic α-secretory pathway. Further, this event is regulated via aromatase-mediated conversion of testosterone to estrogen and the mitogen-activated protein kinase (MAP kinase) signalling pathway. Taken together these data partially elucidates the cellular cascade by which testoterone stimulates sAPP secretion.
ISSN:0304-3940
1872-7972
DOI:10.1016/S0304-3940(00)01622-0