Oestradiol-mediated neuroprotec¬tive signalling mechanisms are activated in various cell types in the brain. Many in vitro studies have shown that oestradiol promotes neuronal survival in primary neurons in the absence of glial cells and that oestradiol directly activates survival mechanisms in neurons55–57. Neurons constitutively express aromatase and therefore are a source of neuroprotective oestradiol. Indeed, oestra¬diol produced by neurons in vitro is neuroprotective58. In addition, some studies suggest that neuronal production of oestradiol may increase under neurodegenerative con¬ditions. For example, it is known that excitotoxic brain injury increases the expression of steroidogenic acute regulatory protein (StAR) in hippocampal neurons, sug¬gesting increased neuronal steroidogenesis under neurodegenerative conditions59 (see BOX 1 for the role of StAR in steroidogenesis).