Analysis of the brain mechanism regulating the reproductive system using small laboratory animals.

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The collaboration is on leading conceptual and technological edges of research in reproductive neuroendocrinology. Our research is being driven by fundamental questions relating to nutrition, growth, and reproductive activity for which we do not have answers. For example, we know that the reproductive system is activated at a specific time during growth in animals and that low nutrition retards growth and delays this activation. However, we are completely ignorant about how the brain knows when growth is sufficient to begin the reproductive process. The most basic elements of this mechanism are not yet understood. After puberty, we know that the reproductive system shuts down during periods of low nutrition, but how the brain senses which nutrients are inadequate is uncertain. We believe that answers to such questions will be forthcoming when we better understand how changes in energy metabolism or reserves are sensed by the brain.The participants through complementary skills, approach … More es, and experimental models are attempting to unravel how metabolic signals are sensed by the brain and routed through neural pathways to regulate the specialized neurons which secrete a unique neuropeptide the controls the entire reproductive system. This peptide, gonadotropin-releasing hormone (GnRH) for which the Nobel prize for Medicine was awarded for its discovery two decades ago, is the single-most important reproductive hormone in the body. Without it, reproduction is not possible in any mammalian species thus far studied. The peptide is not secreted into the peripheral circulation and is only measurable in the microcirculation between the hypothalamus and the pituitary gland which it controls. Its pattern of secretion is generally not measurable in small animal models. However, facilitated by the particular location of the microcirculation in the sheep and goat, the pattern of GnRH can be characterized precisely by a special approach in these large animal models which we will use in this collaboration. Moreover, in these models, electrophysiological correlates of GnRH secretion can be analyzed simultaneously to better understand the neural components of its regulation. On the other hand, the rat is invaluable to study pathways of information transmission and sites of regulation because of the well established stereotaxic approaches and molecular technologies available for this widely used model.We have developped a new concept that energy availability strictly controls the reproductive axis in developing and developed animals. Blood glucose level and its availability are the most important factors regulating physiological events and behavior in the reproduction at various phases. Glucose availability may be sensed centrally and peripherally to regulate reproductive functions as well as feeding behavior, but the location of the sensors and the mechanism of sensing are still unknown. Less