title: Hypoxia and cytoplasmic alkalinization upregulate growth hormone expression in lymphocytes.
abstract: We report here that culture of lymphoid cells under hypoxic conditions showed an increase in both luciferase expression from a GH-promoter luciferase construct and the levels of lymphocyte GH. The effect was mimicked by treatment of cells with cobalt chloride consistent with a specific oxygen-sensing mechanism. We identified a putative hypoxia response element (HRE) in the GH promoter at the region -176 bp to -172 bp that contains a copy of the hypoxia-inducible factor-1 (Hif-1) binding motif (5'-ACGTG-3'). The results also showed that culture of primary rat spleen cells with different doses of TMA induced a dose-dependent increase in lymphocyte GH by Western blot analysis. Greater levels of GH are induced in T cell-enriched populations compared to B cell-enriched populations after treatment with CoCl(2) or TMA. Our results suggest that the stressful cellular conditions likely to occur at sites of inflammation or tumor growth may induce the synthesis of lymphocyte GH.
authors: Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL 35294-0005, USA. Weigent@uab.edu
authors: Douglas A
authors: DA
authors: Weigent
mesh_terms: D000468:Alkalies / Q000737:chemistry; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003035:Cobalt / Q000494:pharmacology; D003593:Cytoplasm / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D013006:Growth Hormone / Q000235:genetics* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D059372:Nucleotide Motifs / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics; D015854:Up-Regulation
chemical_list: D000468:Alkalies; D051793:Hypoxia-Inducible Factor 1; D003035:Cobalt; D013006:Growth Hormone; D008156:Luciferases; C018021:cobaltous chloride
references: Circ Res. 1994 Jun;74(6):1220-6
references: 7514511
references: J Biol Chem. 1973 Jun 25;248(12):4263-8
references: 4711607
references: J Clin Endocrinol Metab. 1993 Apr;76(4):937-9
references: 8473409
references: Genes Dev. 1998 Jan 15;12(2):149-62
references: 9436976
references: Cell Immunol. 2006 Mar;240(1):22-30
references: 16839530
references: J Biol Chem. 2005 Jun 24;280(25):23987-4003
references: 15845533
references: Immunol Rev. 1997 Apr;156:53-66
references: 9176699
references: J Cell Physiol. 1983 Jan;114(1):132-6
references: 6826656
references: J Clin Invest. 1995 May;95(5):2028-34
references: 7738169
references: Endocrinology. 2001 Feb;142(2):767-77
references: 11159849
references: J Neuroimmunol. 2003 Jan;134(1-2):82-94
references: 12507775
references: J Endocrinol. 1995 Dec;147(3):413-22
references: 8543911
references: J Biol Chem. 2001 Jan 19;276(3):2292-8
references: 11056166
references: J Neurochem. 1995 Dec;65(6):2765-72
references: 7595576
references: Ann N Y Acad Sci. 1992 Apr 15;650:179-81
references: 1605473
references: Neuroimmunomodulation. 2004;11(3):149-59
references: 15067206
references: J Neurosci. 2007 Jun 6;27(23):6302-12
references: 17554004
references: Biochim Biophys Acta. 1972 May 16;264(3):472-80
references: 5027627
references: Am J Physiol. 1994 Feb;266(2 Pt 1):C480-8
references: 7511337
references: Circ Res. 1985 Jun;56(6):773-88
references: 2988813
references: Chem Immunol. 1997;69:1-30
references: 9353960
references: Cell Immunol. 1991 Jun;135(1):55-65
references: 2018983
references: Clin Biochem. 1991 Jun;24(3):241-7
references: 1651820
references: Mol Cell Endocrinol. 1995 Sep 22;113(2):225-34
references: 8674830
references: J Biol Chem. 1997 Aug 8;272(32):20055-62
references: 9242677
references: J Biochem. 2004 Sep;136(3):273-7
references: 15598882
references: Nat Rev Cancer. 2002 Jan;2(1):38-47
references: 11902584
references: Brain Behav Immun. 2007 Jan;21(1):79-85
references: 16631346
references: Cancer Microenviron. 2008 Dec;1(1):53-68
references: 19308685
references: Cell Immunol. 2005 Mar;234(1):54-66
references: 15964559
references: J Biol Chem. 2000 Aug 18;275(33):25130-8
references: 10833514
references: Respir Physiol. 1999 Apr 1;115(2):239-47
references: 10385037
references: J Leukoc Biol. 2001 Apr;69(4):522-30
references: 11310837
references: J Mol Endocrinol. 2006 Feb;36(1):1-7
references: 16461922
references: Endocrinology. 1990 Jun;126(6):3271-3
references: 2351117
references: J Appl Physiol (1985). 2000 Apr;88(4):1474-80
references: 10749844
references: Proc Natl Acad Sci U S A. 2004 Oct 19;101(42):15166-71
references: 15353581
references: J Mammary Gland Biol Neoplasia. 2008 Mar;13(1):131-45
references: 18253708
references: Front Biosci. 2005 May 01;10:1239-68
references: 15769622
references: Cell Immunol. 2011;271(1):44-52
references: 21741628
references: J Vasc Res. 2006;43(3):238-50
references: 16449818
references: FASEB J. 2006 May;20(7):828-32
references: 16675839
references: PLoS One. 2007 Dec 26;2(12):e1364
references: 18159247
references: J Biol Chem. 2002 Jun 28;277(26):23111-5
references: 11943784
references: Endocrinology. 2007 Oct;148(10):4533-5
references: 17876033
references: Endocrinology. 1991 Oct;129(4):1727-34
references: 1717238
references: Growth Horm IGF Res. 2006 Oct-Dec;16(5-6):277-89
references: 17101287
references: Annu Rev Pharmacol Toxicol. 2002;42:527-52
references: 11807182
references: Int J Biochem Cell Biol. 2008;40(10):1984-9
references: 17888716
references: Trends Endocrinol Metab. 2001 Aug;12(6):252-7
references: 11445442
references: Mol Endocrinol. 2008 Sep;22(9):2190-202
references: 18635665
references: J Biol Chem. 1996 Jul 26;271(30):17771-8
references: 8663540
references: Arterioscler Thromb Vasc Biol. 2009 May;29(5):665-70
references: 19251587
references: N Engl J Med. 2011 Feb 17;364(7):656-65
references: 21323543
references: J Clin Endocrinol Metab. 1994 Dec;79(6):1678-80
references: 7989474
references: J Neuroimmunol. 2002 Feb;123(1-2):180-7
references: 11880162
references: Cell Immunol. 2009;255(1-2):46-54
references: 19010462
references: Tumour Biol. 1996;17(3):133-54
references: 8638088
references: J Cell Mol Med. 2010 Apr;14(4):771-94
references: 20015196
references: Mol Cell Biol. 1992 Dec;12(12):5447-54
references: 1448077
references: Neuroimmunomodulation. 2000;7(3):126-34
references: 10754400
references: Trends Immunol. 2009 Mar;30(3):102-8
references: 19201652
references: J Biol Chem. 1999 Aug 20;274(34):24147-52
references: 10446188
references: Endocrinology. 2003 Jul;144(7):3182-95
references: 12810575
references: Mol Reprod Dev. 1999 Aug;53(4):398-406
references: 10398415
references: J Clin Endocrinol Metab. 1996 Jul;81(7):2663-9
references: 8675594
references: Neuroendocrinology. 2010;91(1):16-26
references: 20016135
references: Exp Cell Res. 1997 Nov 25;237(1):196-206
references: 9417883