Cross-talk between IGF-I and estradiol in the brain: focus on neuroprotection.
The actions of estradiol in the brain involve the interaction with growth factors, such as insulin-like growth factor-I (IGF-I). Many cells in the brain coexpress receptors for estradiol (ERs) and IGF-I (IGF-IR) and both factors interact to regulate neural function. Several studies have shown that there is an interaction of IGF-IR and ERs in neuroprotection. Neuroprotective effects of estradiol are blocked by the inhibition of IGF-IR signaling, while the neuroprotective effects of IGF-I are blocked by the inhibition of ER signaling. These findings suggest that the neuroprotective actions of estradiol and IGF-I after brain injury depend on the coactivation of both ERs and IGF-IR in neural cells. The relationship of ERalpha with IGF-IR through the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3beta (PI3K/Akt/GSK3) signaling pathway may represent the point of convergence used by estradiol and IGF-I to cooperatively promote neuroprotection. Administration of estradiol to ovariectomized rats results in the association of ERalpha with IGF-IR and with components of the PI3K/Akt/GSK3 signaling pathway and in the regulation of the activity of Akt and GSK3 in the brain. Conversely, IGF-I regulates ERalpha transcriptional activity in neuroblastoma cells and the PI3K/Akt/GSK3 signaling pathway is involved in this effect.
Garcia-Segura
Luis M
LM
Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain. lmgs@cajal.csic.es
Sanz
Amaya
A
Mendez
Pablo
P
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D020239:Receptor Cross-Talk / Q000502:physiology*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D011959:Receptors, Estradiol / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D018696:Neuroprotective Agents; D011959:Receptors, Estradiol; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1