The observation that neuroendocrine peptide hormones are produced by lymphocytes and that cells of the immune system have specific receptors for neuroendocrine hormones now provides a molecular basis for the interactions between the nervous, endocrine, and immune systems. Our present results detecting the production of immunoreactive growth hormone and growth hormone releasing hormone (irGHRH) from lymphocytes is yet another instance in which the immune system is shown to produce hormones commonly found in the neuroendocrine system. GH and GHRH are of particular interest since they are the hormone link between somatic development and its regulation by the central nervous system. The ultimate goal of this project is to determine the biological significance of leukocyte-derived irGH. The early focus in these studies will be to determine whether lymphocyte GH and GHRH- induced biological effects occur in vivo and in vitro. We believe these studies are highly justified based on our results showing that leukocytes do in fact produce GH and GHRH-like peptides. We also plan to study the factors that stimulate or inhibit the production of leukocyte-derived irGH and determine its immunoregulatory activity. Finally, we are proposing to determine the structure of irGH by determining the differences or similarities in the sequences of GH cDNA in leukocytes versus pituitary cells. We will also determine the cDNA sequence of leukocyte-derived irGHRH and compare the similarities to hypothalamic GHRH. We expect the results of these studies will increase our understanding of immunophysiology and establish the role of irGH and irGHRH within the immune system and in the commonality between the neuroendocrine and immune systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS024636-04A1
Application #
3409400
Study Section
Neurology C Study Section (NEUC)
Project Start
1988-02-01
Project End
1994-06-30
Budget Start
1991-07-15
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Alabama Birmingham
Department
Type
Schools of Dentistry
DUNS #
004514360
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Weigent, Douglas A (2013) Expression of lymphocyte-derived growth hormone (GH) and GH-releasing hormone receptors in aging rats. Cell Immunol 282:71-8
Arnold, Robyn E; Weigent, Douglas A (2003) The production of nitric oxide in EL4 lymphoma cells overexpressing growth hormone. J Neuroimmunol 134:82-94
Arnold, Robyn E; Weigent, Douglas A (2003) The inhibition of superoxide production in EL4 lymphoma cells overexpressing growth hormone. Immunopharmacol Immunotoxicol 25:159-77
Weigent, D A; Vines, C R; Long, J C et al. (2000) Characterization of the promoter-directing expression of growth hormone in a monocyte cell line. Neuroimmunomodulation 7:126-34
Vines, C R; Weigent, D A (2000) Identification of SP3 as a negative regulatory transcription factor in the monocyte expression of growth hormone. Endocrinology 141:938-46
Weigent, D A (1996) Immunoregulatory properties of growth hormone and prolactin. Pharmacol Ther 69:237-57
Rohn, W M; Weigent, D A (1995) Cloning and nucleotide sequencing of rat lymphocyte growth hormone cDNA. Neuroimmunomodulation 2:108-14
Weigent, D A; Blalock, J E (1995) Associations between the neuroendocrine and immune systems. J Leukoc Biol 58:137-50
Payne, L C; Weigent, D A; Blalock, J E (1994) Induction of pituitary sensitivity to interleukin-1: a new function for corticotropin-releasing hormone. Biochem Biophys Res Commun 198:480-4
Law, V; Payne, L C; Weigent, D A (1994) Effects of streptozotocin-induced diabetes on lymphocyte POMC and growth hormone gene expression in the rat. J Neuroimmunol 49:35-44

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