Reproduction, an essential function for perpetuation of the species, is under the control of a sophisticated network of regulatory signals, which include nutritional cues and metabolic factors. Disorders of reproductive maturation (puberty) and function are becoming increasingly common in Europe, and other developed countries, and appear to be linked to the rapid increase in metabolic disorders within the community ranging from energy insufficiency to obesity. It is suspected that information on metabolic status is integrated into the control of fertility at the level of the GnRH neuron, the key cell regulating fertility in all mammalian species. How this occurs is not known. The global aim of this project is to gain insight into the neuroendocrine and molecular mechanisms responsible for the metabolic regulation of puberty and fertility, and their eventual alteration in conditions of disturbed energy balance. To this end, a combination of in vivo and ex vivo approaches, using conventional and genetically-modified rodent models, will be implemented in order to evaluate (i) the effects of selected metabolic hormones (ghrelin) and metabolic neuropeptidergic pathways (NPY, AgRP, alpha-MSH) on GnRH neuronal activation, and (ii) to analyze the putative role of the sensor of intracellular energy status, mTOR, in mediating the actions of the above signals on GnRH neurons. It is anticipated that implementation of the project will expand greatly our knowledge of the physiological and pathophysiological mechanisms underlying the metabolic control of reproduction. In addition, completion of the proposed workplan will allow the applicant to get acquainted with powerful genetic methodological tools that will strengthen further his experience in neuroendocrinology, boosting his future research career and paving the way for closer scientific collaborations between the outgoing and return Institutions.