Relationship between the neuroprotective effects of insulin-like growth factor-1 and 17β-oestradiol in human neuroblasts.

Insulin-like growth factor-1 (IGF-1) and oestrogens interact with each other as neuroprotective factors. We have previously demonstrated that 17β-oestradiol protects against β-amyloid and oxidative stress toxicity and increases the amount of cell cholesterol in human foetal neuroblasts (FNC). The present study aimed: (i) to assess the protective effects of IGF-1 in FNC cells; (ii) to investigate the relationship between IGF-1 and 17β-oestradiol; and (iii) to determine whether cholesterol was a major mediator of the effects of IGF-1, similarly to 17β-oestradiol. We found that IGF-1 effectively exerts neuroprotective effects in FNC cells. We also demonstrated that the IGF-1 receptor (IGF-1R) pathway is needed to maintain oestrogen-mediated neuroprotection. Finally, we found that, opposite to 17β-oestradiol, IGF-1 did not cause a significant increase in cell cholesterol. These findings indicate that a cross-talk between IGF-1 and 17β-oestradiol occurs in FNC cells. In particular, the activation of the IGF-1R cascade appears to be fundamental to warrant 17β-oestradiol-mediated neuroprotection, even though cell cholesterol does not play a major role as an effector of this pathway.