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.
Cardona-Gomez
Gloria Patricia
GP
Instituto Cajal, C.S.I.C., Av. Dr. Arce 37, 28002 Madrid, Spain.
Mendez
Pablo
P
Garcia-Segura
Luis Miguel
LM
D000818:Animals; D004347:Drug Interactions / Q000502:physiology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000187:drug effects / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010052:Ovariectomy; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar
D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; C494920:Akt1 protein, rat