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

doi:10.1016/S0304-3940(00)01622-0

Neuroscience Letters

Volume 296, Issue 1, 15 December 2000, Pages 49-52

https://doi.org/10.1016/S0304-3940(00)01622-0 Get rights and content

Abstract

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.

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Acknowledgements

We thank Dr R. Weiner for providing the GT1–7 cell line. This work was supported in part by the DFG-Grant BE 1475/2-1 to C.B.

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

Abstract

Section snippets

Acknowledgements

Trends Pharmacol. Sci.

J. Biol. Chem.

J. Biol. Chem.

Neurosci. Lett.

Neuroprotection against oxidative stress by estrogens: structure-activity relationship

Mol. Pharmacol.

The tyrosine kinase and mitogen-activated protein kinase pathways mediate multiple effects of estrogen in hippocampus

Proc. Natl. Acad. Sci.

Regulation of secretion of Alzheimer amyloid precursor protein by the mitogen-activated protein kinase cascade

J. Neurochem.