Interactions of estradiol and insulin-like growth factor-I signalling in the nervous system: new advances.

Estradiol and insulin-like growth factor-I (IGF-I) interact in the brain to regulate a variety of developmental and neuroplastic events. Some of these interactions are involved in the control of hormonal homeostasis and reproduction. However, the interactions may also potentially impact on affection and cognition by the regulation of adult neurogenesis in the hippocampus and by promoting neuroprotection under neurodegenerative conditions. Recent studies suggest that the interaction of estradiol and IGF-I is also relevant for the control of cholesterol homeostasis in neural cells. The molecular mechanisms involved in the interaction of estradiol and IGF-I include the cross-regulation of the expression of estrogen and IGF-I receptors, the regulation of estrogen receptor-mediated transcription by IGF-I and the regulation of IGF-I receptor signalling by estradiol. Current investigations are evidencing the role exerted by key signalling molecules, such as glycogen synthase kinase 3 and beta-catenin, in the cross-talk of estrogen receptors and IGF-I receptors in neural cells.