INTERACTION OF INSULIN-LIKE GROWTH-FACTOR-I AND ESTRADIOL SIGNALING PATHWAYS ON HYPOTHALAMIC NEURONAL DIFFERENTIATION

Neurotrophic effects of estradiol and insulin-like growth factor-I wer e assessed in primary cultures from fetal rat hypothalamus. Cultured n eurons were immunostained with an antibody for the microtubule-associa ted protein-2. While both estradiol and insulin-like growth factor-I i ncreased the number of microtubule-associated protein-2-immunoreactive neurons and the extension of immunoreactive processes, the effect of these two factors was not additive. The estradiol-induced increases in neuronal numbers and extension of neuronal processes were blocked by either the estrogen receptor antagonist ICI 182,780 or by an anti-sens e oligonucleotide to the estrogen receptor. Furthermore, incubation of the cultures with an anti-sense oligonucleotide directed against the insulin-like growth factor-I messenger RNA also blocked the effect of estradiol. In turn, the effects of insulin-like growth factor-I were b locked by the estrogen receptor antagonist ICI 182,780 and by the anti -sense oligonucleotide to the estrogen receptor. These findings sugges t that estradiol-induced activation of the estrogen receptor in develo ping hypothalamic cells requires the presence of insulin-like growth f actor-I, and that both estradiol and insulin-like growth factor-I use the estrogen receptor as a mediator of their trophic effects on hypoth alamic neurons. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.