METABOLIC TARGETING OF GnRH NEURONS: MOLECULAR MECHANISMS AND NEUROPEPTIDE PATHWAYS.
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.
Role of the andalusian partner
The group UCO is the coordinator of this Project. The research fellow associated to this project will conduct part of his activities at the UCO group (during the return phase of his fellowship), where he will continue physiologic studies on the neuro-endocrine mechanisms for the metabolic control of GnRH secretion and, hence, of puberty onset and fertility.
Impact
This project will provide novel physiological knowledge on the mechanisms governing key reproductive phenomena, including puberty onset and reproduction, with special emphasis on elucidation of the basis for their metabolic modulation. Considering the increasing incidence of disturbances of puberty and fertility in the general population, it is expected that the results of this project will help to unveil part of the neuroendocrine and molecular mechanisms for such alterations. While this information will be generated using suitable animal models, our results are posed with potential translational interest, as to illustrate on the putative basis of human reproductive diseases.