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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
3R01HD019731-03S1
Application #
3317198
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1984-12-01
Project End
1988-06-30
Budget Start
1987-12-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Emory University
Department
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Tigges, J; McDonald, J K; Tigges, M et al. (1997) Neuropeptide Y in the infundibular nucleus and hypophysis of great apes. Cell Tissue Res 290:665-8
McDonald, J; Calka, J (1994) Relationship between neuropeptide Y and luteinizing-hormone-releasing hormone immunoreactivities in the hypothalamus and preoptic region. Acta Anat (Basel) 151:171-9
Sabatino, F D; Collins, P; McDonald, J K (1990) Investigation of the effects of progesterone on neuropeptide Y-stimulated luteinizing hormone-releasing hormone secretion from the median eminence of ovariectomized and estrogen-treated rats. Neuroendocrinology 52:600-7
McDonald, J K (1990) Role of neuropeptide Y in reproductive function. Ann N Y Acad Sci 611:258-72
Lumpkin, M D; McDonald, J K (1989) Blockade of growth hormone-releasing factor (GRF) activity in the pituitary and hypothalamus of the conscious rat with a peptidic GRF antagonist. Endocrinology 124:1522-31
McDonald, J K; Lumpkin, M D; DePaolo, L V (1989) Neuropeptide-Y suppresses pulsatile secretion of luteinizing hormone in ovariectomized rats: possible site of action. Endocrinology 125:186-91
Tigges, M; Tigges, J; McDonald, J K et al. (1989) Postnatal development of neuropeptide Y-like immunoreactivity in area 17 of normal and visually deprived rhesus monkeys. Vis Neurosci 2:315-28
Sabatino, F D; Collins, P; McDonald, J K (1989) Neuropeptide-Y stimulation of luteinizing hormone-releasing hormone secretion from the median eminence in vitro by estrogen-dependent and extracellular Ca2+-independent mechanisms. Endocrinology 124:2089-98
McDonald, J K; Han, C; Noe, B D et al. (1988) High levels of NPY in rabbit cerebrospinal fluid and immunohistochemical analysis of possible sources. Brain Res 463:259-67
McDonald, J K; Tigges, J; Tigges, M et al. (1988) Developmental study of neuropeptide Y-like immunoreactivity in the neurohypophysis and intermediate lobe of the rhesus monkey (Macaca mulatta). Cell Tissue Res 254:499-509

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