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Front Neuroendocrinol. 2006 Dec;27(4):391-403. Epub 2006 Oct 16.

Cross-talk between estrogen receptors and insulin-like growth factor-I receptor in the brain: cellular and molecular mechanisms.

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  • 1Instituto Cajal, Consejo Superior de Investigaciones Científicas (CSIC), E-28002 Madrid, Spain.


Accumulating evidence suggests that insulin-like growth factor-I (IGF-I) and estradiol interact to regulate neural function. In this review, we focus on the cellular and molecular mechanisms involved in this interaction. The expression of estrogen receptors (ERs) and IGF-I receptor is cross-regulated in the central nervous system and many neurons and astrocytes coexpress both receptors. Furthermore, estradiol activates IGF-I receptor and its intracellular signaling. This effect may involve classical ERs since recent findings suggest that ERalpha may affect IGF-I actions in the brain by a direct interaction with some of the components of IGF-I signaling. In turn, IGF-I may regulate ER transcriptional activity in neuronal cells. In conclusion, ERs appear to be part of the signaling mechanism of IGF-I, and IGF-I receptor part of the mechanism of estradiol signaling in the nervous system.

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