Testosterone exerts neuroprotective effects on the brain, but the mechanisms by which these effects are exerted appear to be different in males and females. While in females they involve local convers Show more
Testosterone exerts neuroprotective effects on the brain, but the mechanisms by which these effects are exerted appear to be different in males and females. While in females they involve local conversion to estradiol, in males they may be androgen receptor-dependent, or mediated through metabolism to neurosteroids such as 5α-androstane-3α,17β-diol (3α-diol), which acts through different mechanisms than testosterone itself. Recently, we demonstrated that 3α-diol can protect neurons and neuronal-like cells against oxidative stress-induced neurotoxicity associated with prolonged phosphorylation of the extracellular signal-regulated kinase (ERK). The mechanism(s) responsible for these effects remain unknown. In the present study, we sought to determine whether the ERK-specific phosphatase, mitogen-activated protein kinase phosphatase 3/dual specificity phosphatase 6 (MKP3/DUSP6), is involved in the cytoprotective effects of 3α-diol in SH-SY5Y human female neuroblastoma cells. 3α-diol inhibited ERK phosphorylation and ameliorated cell death induced by the oxidative stressor hydrogen peroxide (H Show less