Melatonin, the mammalian pineal gland hormone, synthesized during the dark phase, shows a circadian and seasonal rhythm. Its synthesis is synchronized to the light/dark cycle and to seasonal photoperiod informations through the year, which is transmitted to the gland through the retino-hypothalamic pathway. Melatonin synthesis is induced by norepinephrine release in the gland perivascular space at night, also modulated by peptidergic systems, for example, neuropeptide Y, vasoactive intestinal polipeptide (VIP), Pituitary adenylate cyclase-activating peptide (PACAP), moreover, recent publication has shown a important role of insulin on the modulation of melatonin synthesis. Norepinephrine and Insulin modulate the key-enzyme activities involved on melatonin synthesis, tryptophan hydroxylase (TPOH) and arylalkylamine-N-acetyltransferase (AANAT) through pos transcriptional mechanisms. Conserning insulin's important role on melatonin synthesis induced by norepinephrine, the aim of this project is to study the insulin signaling pathway norepinephrine-mediated in the presence or absence of specific norepinephrine antagonists alpha 1 and beta 1 within pineal gland, analysing: protein and state of insulin receptor, insulin receptor substrates,PI3-K, AKT and MAPKs.
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