Cross-Talk between IGF-I and Estradiol in the Brain: Focus on NeuroprotectionGarcia-Segura L.M. · Sanz A. · Mendez P.
aInstituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain; bDépartement des Neurosciences Fondamentales, Centre Médical Universitaire, Geneva, Switzerland
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 ERα with IGF-IR through the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3β (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 ERα 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 ERα transcriptional activity in neuroblastoma cells and the PI3K/Akt/GSK3 signaling pathway is involved in this effect.
Luis M. Garcia-Segura
Instituto Cajal, CSIC, Avenida Doctor Arce 37
ES–28002 Madrid (Spain)
Tel. +34 91 585 4729, Fax +34 91 585 4754
Presented at the Sixth International Congress of Neuroendocrinology, June 19–22, 2006, Pittsburgh, Pa., USA.
Received: October 16, 2006
Accepted: October 17, 2006
Published online: November 23, 2006
Number of Print Pages : 5
Number of Figures : 1, Number of Tables : 0, Number of References : 58
Neuroendocrinology (International Journal for Basic and Clinical Studies on Neuroendocrine Relationships)
Vol. 84, No. 4, Year 2006 (Cover Date: February 2007)
Journal Editor: Millar, R. (Edinburgh)
ISSN: 0028–3835 (print), 1423–0194 (Online)
For additional information: http://www.karger.com/NEN