Objectives: The long-term objectives are to explore the role of NPY in reproductive neuroendocrine processes in the rat by examining the following hypothesis: 1) that the observed effects of NPY to inhibit luteinizing hormone secretion (see Preliminary Studies) are mediated through effects on hypothalamic catecholamines and/or LHRH secretion and 2) hypothalamic NPY containing neurons are responsive to changes in gonadal steroids. The proposed research addresses fundamental questions concerning NPY, a peptide found in the rat and human brain in higher concentration than any peptide previously described and should yield important data about its involvement in reproductive neuroendocrine processes such as the control of LH secretion.
Aims : 1. To precisely determine the anatomical relationships which may exist between NPY and LHRH or catecholamine containing cell bodies and terminals, antisera to NPY will be generated in rabbits and immunohistochemical methods will be used to investigate the distribution of labeled cell bodies and terminals in the hypothalamus and pituitary gland. Results will be compared with descriptions of LHRH and catecholaminergic neuronal cell bodies and terminals. 2. Hypothalamic and pituitary homogenates will be examined for the presence of receptors which will bind iodinated NPY in a saturable and reversible manner. 3. To examine the hypothesis that NPY inhibits LH release through effects on hypothalamic catecholamines and/or LHRH secretion, hypothalamic fragments and slices will be perfused with medium containing NPY. The perfusate and tissue fragments will be collected and analyzed by RIA and HPLC with ultraviolet and electrochemical detection for changes in LHRH and catecholamines. 4. Potential direct effects of NPY on luteotrophs will be determined using perfused columns of anterior pituitary cells exposed to NPY with or without LHRH. 5. To explore the hypothesis that hypothalamic NPY neurons are responsive to changes in serum levels of gonadal steroids, male and female rats will be sacrificed at various times after gonadectomy and steroid replacement. Regions of the hypothalamus will be analyzed for changes in the concentration of NPY using RIA and HPLC.
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