Our goals are to elucidate the mechanisms underlying release of LH- releasing hormone (LHRH) from hypothalamic neurons and its regulation by steroids. Our studies led to the formulation of this working hypothesis: Copper (Cu), co-released with norepinephrine (NE) or a-amidated peptides, modulates LHRH relaease; one such action of Cu is the amplification of prostaglandin E2 (PGE2) stimulation of LHRH release. Adrenal steroids exert a positive input on LHRH relaease in the maturing male rat, by regulating the plasma-membrane machinery involved in the process of Cu- amplified PGE2 (Cu/PGE2) stimulation of LHRH release and by regulating Cu release from neurons impinging on the LHRH neuron. S.A.1 is to elucidate the mechanism(s) by which Cu modulates LHRH release; using explants of the median eminence as a model. We will investigate (i) whether and how a CuNE complex mixture stimulates LHRH release; (ii) whether Cu amplification of PGE2 stimulation of LHRH release is a result of Cu interaction with the opioid receptor and/or Cu inhibition of cAMP efflux. S.A.2. is to elucidate the mechanism(s) underlying adrenal regulation of LHRH release in the maturing male rat; specifically Cu/PGE2- stimulated release. We will (i) characterize the ontogeny of the positive feedback of adrenals steroids on LHRH release and identify the regulatory steroid; (ii) examine the specificity of steroid action on Cu/PGE2 -stimulated release of LHRH by examining the effects on CuHis-, veratridine- and K- induced release; and (iii) study the effect of steroids on the kinetic parameters of Cu and PGE2 interactive sites ad on uptake and release of 67-Cu in various brain regions. S.A3. is to elucidate the biochemical mechanisms underlying Cu homeostasis in the hyothalamus; uptake, release, and intracellular processing. We will (i) further establish the process of 67-Cu release, using veratridine (Na-influx) induced release as a model; (ii) analyse the kinetics of 67-Cu uptake into the releasable pool of Cu; and (iii) study the intracellular processing of newly taken-up CuHis, specifically ligand exchange of the His. Understanding the mechanisms underlying Cu action on the LHRH neuron and steroid regulation of LHRH release in teh maturing male, will provide insight into integrative regulatory processes in the brain and into developmental and hormonally regulated brain functions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK025692-11
Application #
3227537
Study Section
Endocrinology Study Section (END)
Project Start
1978-06-01
Project End
1993-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
11
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Texas Sw Medical Center Dallas
Department
Type
Schools of Medicine
DUNS #
City
Dallas
State
TX
Country
United States
Zip Code
75390
Lin, Henry C; Chey, William Y (2003) Cholecystokinin and peptide YY are released by fat in either proximal or distal small intestine in dogs. Regul Pept 114:131-5
Jin, H O; Zhou, L; Lee, K Y et al. (1996) Inhibition of acid secretion by electrical acupuncture is mediated via beta-endorphin and somatostatin. Am J Physiol 271:G524-30
Chang, C H; Chey, W Y; Braggins, L et al. (1996) Pituitary adenylate cyclase-activating polypeptide stimulates cholecystokinin secretion in STC-1 cells. Am J Physiol 271:G516-23
Lee, K Y; Krusch, D; Zhou, L et al. (1995) Effect of endogenous insulin on pancreatic exocrine secretion in perfused dog pancreas. Pancreas 11:190-5
Yegen, B; Biren, T; Onat, F et al. (1995) Modulation of gallbladder contraction by pirenzepine in humans. Am J Gastroenterol 90:1489-94
Chang, C H; Chey, W Y; Coy, D H et al. (1995) Galanin inhibits cholecystokinin secretion in STC-1 cells. Biochem Biophys Res Commun 216:20-5
Barnea, A; Cho, G; Lu, G (1994) Role for glial cells in regulating the functional expression of neuropeptide Y (NPY) neurons in aggregate cultures derived from dissociated fetal brain cells. J Neurosci Res 38:459-67
Lee, K Y; Lee, Y L; Kim, C D et al. (1994) Mechanism of action of insulin on pancreatic exocrine secretion in perfused rat pancreas. Am J Physiol 267:G207-12
Sztefko, K; Li, P; Ballatori, N et al. (1994) CCK-receptor antagonists proglumide and loxiglumide stimulate bile flow and biliary glutathione excretion. Dig Dis Sci 39:1974-80
Jin, H O; Lee, K Y; Chang, T M et al. (1994) Secretin: a physiological regulator of gastric emptying and acid output in dogs. Am J Physiol 267:G702-8

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