Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 77, Issue 5, pages 1319–1326, June 2001
How to Cite
Hammond, J., Le, Q., Goodyer, C., Gelfand, M., Trifiro, M. and LeBlanc, A. (2001), Testosterone-mediated neuroprotection through the androgen receptor in human primary neurons. Journal of Neurochemistry, 77: 1319–1326. doi: 10.1046/j.1471-4159.2001.00345.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received January 24, 2001; accepted March 5, 2001.
- Alzheimer's disease;
- human primary neurons
Estrogen is an active neuroprotectant and is presently investigated as a potential therapy against Alzheimer's disease for women. To determine if male hormones could also be neuroprotective, we investigated the effect of testosterone, methyltestosterone, and epitestosterone at physiological concentrations on primary cultures of human neurons induced to undergo apoptosis by serum deprivation. Serum deprivation significantly induces neuronal apoptosis in a protracted fashion. As expected, physiological concentrations of 17-β-estradiol and transcriptionally inactive 17-α-estradiol protect neurons against apoptosis. Similar to 17-β-estradiol, physiological concentrations of testosterone are also neuroprotective. Androgen receptors are present at 8 ± 2 fmol/mg protein in the neuron cultures. The non-aromatizable androgen, mibolerone, is also neuroprotective and aromatase inhibitor, 4-androsten-4-OL-3,17-dione, does not prevent testosterone-mediated neuroprotection. In contrast, anti-androgen, flutamide, eliminates testosterone-mediated neuroprotection. Testosterone analog, methyltestosterone, showed androgen receptor-dependent neuroprotection that was delayed in time indicating that a metabolite may be the active agent. The endogenous anti-androgen, epitestosterone, also showed a slight neuroprotective effect but not through 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.