title: Interaction of insulin-like growth factor-I and estradiol signaling pathways on hypothalamic neuronal differentiation.
abstract: Neurotrophic effects of estradiol and insulin-like growth factor-I were assessed in primary cultures from fetal rat hypothalamus. Cultured neurons were immunostained with an antibody for the microtubule-associated protein-2. While both estradiol and insulin-like growth factor-I increased 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-sense 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 blocked by the estrogen receptor antagonist ICI 182,780 and by the anti-sense oligonucleotide to the estrogen receptor. These findings suggest that estradiol-induced activation of the estrogen receptor in developing hypothalamic cells requires the presence of insulin-like growth factor-I, and that both estradiol and insulin-like growth factor-I use the estrogen receptor as a mediator of their trophic effects on hypothalamic neurons.
authors.affiliation: Instituto Cajal, C.S.I.C., Madrid, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Duenas
authors.forename: I
authors.initials: I
authors.lastname: Torres-Aleman
authors.forename: F
authors.initials: F
authors.lastname: Naftolin
authors.forename: L M
authors.initials: LM
authors.lastname: Garcia-Segura
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004958:Estradiol; D007334:Insulin-Like Growth Factor I