Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons

Citation
J. Hammond et al., Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons, J NEUROCHEM, 77(5), 2001, pp. 1319-1326
Citations number
65
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROCHEMISTRY
ISSN journal
0022-3042 → ACNP
Volume
77
Issue
5
Year of publication
2001
Pages
1319 - 1326
Database
ISI
SICI code
0022-3042(200106)77:5<1319:TNTTAR>2.0.ZU;2-X
Abstract
Estrogen is an active neuroprotectant and is presently investigated as a po tential therapy against Alzheimer's disease for women. To determine if male hormones could also be neuroprotective, we investigated the effect of test osterone, methyltestosterone, and epitestosterone at physiological concentr ations on primary cultures of human neurons induced to undergo apoptosis by serum deprivation. Serum deprivation significantly induces neuronal apopto sis in a protracted fashion. As expected, physiological concentrations of 1 7-beta -estradiol and transcriptionally inactive 17-alpha -estradiol protec t neurons against apoptosis. Similar to 17-beta -estradiol, physiological c oncentrations of testosterone are also neuroprotective. Androgen receptors are present at 8 +/- 2 fmol/mg protein in the neuron cultures. The non-arom atizable androgen, mibolerone, is also neuroprotective and aromatase inhibi tor, 4-androsten-4-OL-3,17-dione, does not prevent testosterone-mediated ne uroprotection. In contrast, anti-androgen, flutamide, eliminates testostero ne-mediated neuroprotection. Testosterone analog, methyltestosterone, showe d androgen receptor-dependent neuroprotection that was delayed in time indi cating that a metabolite may be the active agent. The endogenous anti-andro gen, epitestosterone, also showed a slight neuroprotective effect but not t hrough the androgen receptor. These results indicate that androgens induce neuroprotection directly through the androgen receptor. These data suggest that androgens may also be of therapeutic value against Alzheimer's disease in aging males.