Trophic Effects of Estradiol on Hypothalamic Neurons are Mediated by IGFI

We have recently studied whether the effects of estrogen on hypothalamic neuronal survival and neurite growth are mediated by IGF-I (82). Hypothalamic cultures exposed to estradiol or IGF-I showed a significant increase in neuronal survival and in the growth of MAP-2 immunoreactive processes. The simultaneous incubation of cultures with 17^-estradiol and IGF-I also resulted in increased neuronal survival and differentiation. The effect of estradiol and IGF-I acting together was similar to that observed when cultures were treated separately with either factor. Therefore, the effects of 17^-estradiol and IGF-I were not additive, suggesting that both factors may be acting through a common mechanism. We decided to test whether the effect of estradiol was dependent on IGF-I synthesis. Incubation of the cultures with an antisense oligonucleotide to IGF-I resulted in a significant decrease in the stimulatory effects of 17^-estradiol on the number of neurons and the extension of neuronal processes (82). These results indicate that IGF-I synthesis in the cultures is necessary for the manifestation of the sex steroid effect, suggesting that estradiol may induce neuronal survival and differentiation by the activation of IGF-I signaling cascades.

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