The proposed neuroanatomical studies employ immunohistochemical and hybridization histochemical methods to clarify the roles of particular hormonal and neural influences in regulating the expression of multiple neuroactive peptides that cohabit neurosecretory neuron populations in the rat hypothalamus. Parvocellular neurons that produce corticotropin-releasing factor for the initiation of pituitary-adrenal responses to stress, and magnocellular neurosecretory neurons that synthesize the peptide hormones oxytocin or vasopressin (which play roles reproduction and body water balance, respectively), are both known to express a number of additional neuropeptides. Differential effects of alterations in steroid hormones status have been described for both class of neurons. The proposed studies will address the following issues: 1. Non-steroidal influences on the CRF neuron. Evidence for roles of circulating corticotropin, thyroid hormones, and as yet unspecified stimuli associated with lactation will be characterized as to their effects on levels of co-existing peptides, their sites of action and/or whether effects on gene expression are involved. 2. Role of neural inputs in influencing peptide expression in the CRF neuron. The roles of projections arising from brainstem catecholamine neurons, the hippocampal formation, and the basal forebrain in mediating peptide dynamics in the CRF neuron, and or in mediating the feedback effects of steroids will be assessed. The role of aminergic pathways in mediating responses to a specific stress model (hemorrhage) will also be evaluated. 3. Gonadal steroid effects on the magnocellular system. We have described pronounced and selective effects of manipulation of gonadal hormone status on the expression of coexisting peptides in magnocellular neurosecretory neurons of female rats. Systemic steroid replacement studies will be carried out in gonadectomized male rats to evaluate the generality and steroid specificity of the effect. Combined retrograde-transport -immunohistochemical methods will be used to determine whether the effect is specific to magnocellular neurons.
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