Synergistic interaction of estradiol and insulin-like growth factor-I in the activation of PI3K/Akt signaling in the adult rat hypothalamus

Estradiol and insulin-like growth factor-I (IGF-I) interact in the hypothalamus to regulate neuronal function, synaptic plasticity and neuroendocrine events. However, the molecular mechanisms involved in these interactions are still unknown. In the present study, the effect of estradiol on the signaling pathways of IGF-I receptor has been assessed in the hypothalamus of young adult ovariectomized rats, using specific antibodies for the phosphorylated forms of extracellular-signal regulated kinase (ERK) 1 and ERK2 and Akt/protein kinase B (Akt/PKB). Estradiol treatment resulted, between 6 and 24 h after systemic administration, in dose-dependent effects on the phosphorylation of ERK and Akt/PKB. Estradiol did not modify the level of ERK phosphorylation induced by intracerebroventricular administration of IGF-I. However, both hormones had a synergistic effect on the phosphorylation of Akt/PKB. These findings suggest that estrogen effects in the hypothalamus may be mediated in part by the activation of the signaling pathways of the IGF-I receptor. (C) 2002 Elsevier Science B.V. All rights reserved.