The actions of oestradiol in the brain involve interaction with growth factors, such as insulin-like growth factor-I (IGF-I). Many cells in the brain co-express receptors for oestradiol and IGF-I and both factors interact to regulate neural function. The relationship of oestrogen receptor a with IGF-I receptor through the mitogen-activated protein kinase and the phosphomositide 3-kinase signalling pathways may represent the point of convergence used by these two factors to cooperatively modulate neuritic growth, synaptic plasticity, neuroendocrine events, reproductive behaviour and neuronal survival. In addition, Akt and glycogen synthase kinase 3 beta are key molecular targets to explain the interaction of oestrogen and IGF-I receptor signalling in the promotion of neuroprotection.