The focus of this proposal is to determine the roles the recently described prolactin releasing peptides (PrRPs) may play in stress-induced elevations of prolactin secretion (neuroendocrine actions in pituitary gland and neuromodulatory actions in brain) and autonomic function (neuromodulator actions in brain). We hypothesize that the PrRPs produced in brain and pituitary gland are required for the normal neuroendocrine and cardiovascular responses to stress. Specifically we hypothesize that PrRPs, either produced locally in pituitary gland or delivered to the gland via either the portal or peripheral circulations, play a role in the secretion of prolactin from the gland during stress. Furthermore, we hypothesize that the elevation in sympathetic tone during stress depends upon the actions of brain-derived PrRPs and that removal of those peptides will compromise the animal's cardiovascular response to stress. We will address the following Specific Aims (Questions): 1) Will physical or anticipatory stress elevate circulating plasma levels of PrRP, tissue levels of the peptides (brain, pituitary, adrenal), or expression of the gene (mRNA levels) in brain, pituitary gland or adrenal medulla? 2) Are the PrRPs effective releasing factors in the setting of dopamine withdrawal (which occurs in stress)? 3) Will central administration of PrRP stimulate prolactin secretion in conscious animals? 4) Can the site of action of PrRP in brain be identified by site-specific injections? 5) Will compromise of endogenous PrRP alter the neuroendocrine and cardiovascular responses to stress? The studies described here are designed to further characterize the pharmacology and physiology of the PrRPs, which have been demonstrated to act in the pituitary as neuroendocrine factors and in brain as modulators of autonomic outflow. The ultimate goal is to determine their importance in the maintenance of normal endocrine and cardiovascular function, in particular during stress. These studies will also begin to examine a potentially novel confluence of endocrine and autonomic responses to stress and thereby provide insight into the coordinated responses of multiple organ systems to stress.
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