NEUROPEPTIDE CO-EXPRESSION IN THE HYPOTHALAMUS

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The proposed neuroanatomical studies are designed to test the hypothesis that alterations in steroid hormone status can effect pronounced changes in the cellular localization, and co-localization, of neuropeptides in the mammalian hypothalamus. Immunohistochemical double-staining methods will be used to assay the responses of biochemically- and functionally-specified pools of neurons in the paraventricular nucleus of the hypothalamus (PVH) to various endocrine manipulations. We have described on adrenal steroid-dependent co-expression corticotropin releasing factor (CRF)- and vasopressin-immunoreactivity (IR) in parvocellular neurosecretory neurons and preliminary studies suggest that the same two peptides may be expressed in magnocellular neurosecretory neurons in estrogen-treated ovariectomized rats. Additional study is required to characterize these phenomena by determining: (i) whether these responses to manipulation of steroid hormone status are specific to CRF- and vasopressin-IR, (ii) the identity of the steroids that mediate these responses, (iii) the site(s) within the brain at which steroids act to influence peptide expression, (iv) the role of neural inputs to the PVH in mediating steroid-dependent and steroid-independent changes in peptide expression, and (v) whether the co-expression of CRF- and vasopressin-IR in parvocellular and magnocellular neurosecretory neurons occur over the course of normal fluctuations in adrenal and ovarian steroid titers. Collectively, these studies should establish the existence of a plasticity in the expression of neuropeptides by neuroendocrine neurons as a function of physiological state. This may prove to be an important organizing principle in hypothalamic circuitry that serves to maintain homeostasis. The peptides in question play well-recognized roles in such essential and health-related processes as the regulation of the cardiovascular system, the protection of the organism from stress and the control of reproductive function.