title: GATA augments GNRH-mediated increases in Adcyap1 gene expression in pituitary gonadotrope cells.
abstract: Pituitary adenylate cyclase-activating polypeptide 1 (PACAP or ADCYAP1) regulates gonadotropin biosynthesis and secretion, both alone and in conjunction with GNRH. Initially identified as a hypothalamic-releasing factor, ADCYAP1 subsequently has been identified in pituitary gonadotropes, suggesting it may act as an autocrine-paracrine factor in this tissue. GNRH has been shown to increase pituitary Adcyap1 gene expression through the interaction of CREB and jun/fos with CRE/AP1 cis-elements in the proximal promoter. In these studies, we were interested in identifying additional transcription factors and cognate cis-elements which regulate Adcyap1 gene promoter activity and chose to focus on the GATA family of transcription factors known to be critical for both pituitary cell differentiation and gonadotropin subunit expression. By transient transfection and electrophoretic mobility shift assay analysis, we demonstrate that GATA2 and GATA4 stimulate Adcyap1 promoter activity via a GATA cis-element located at position -191 in the rat Adcyap1 gene promoter. Furthermore, we show that addition of GATA2 or GATA4 significantly augments GNRH-mediated stimulation of Adcyap1 gene promoter activity in the gonadotrope LβT2 cell line. Conversely, blunting GATA expression with specific siRNA inhibits the ability of GNRH to stimulate ADCYAP1 mRNA levels in these cells. These data demonstrate a complex interaction between GNRH and GATA on ADCYAP1 expression, providing important new insights into the regulation of gonadotrope function.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9032, USA.
authors.forename: Robin L
authors.initials: RL
authors.lastname: Thomas
authors.forename: Natalie M
authors.initials: NM
authors.lastname: Crawford
authors.forename: Constance M
authors.initials: CM
authors.lastname: Grafer
authors.forename: Weiming
authors.initials: W
authors.lastname: Zheng
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Halvorson
mesh_terms: D000818:Animals; D002460:Cell Line; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D052681:Gonadotrophs; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000378:metabolism*; D010902:Pituitary Gland; D011401:Promoter Regions, Genetic / Q000235:genetics; D034741:RNA, Small Interfering
chemical_list: D050989:GATA2 Transcription Factor; D050991:GATA4 Transcription Factor; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D034741:RNA, Small Interfering; D007987:Gonadotropin-Releasing Hormone
keywords: GATA; PACAP; adenylate cyclase-activating polypeptide 1; gonadotropes; pituitary
references.citation: Regul Pept. 2011 Apr 11;167(2-3):227-32
references.pmid: 21329727
references.citation: Endocrinology. 2001 Sep;142(9):3828-35
references.pmid: 11517159
references.citation: J Clin Endocrinol Metab. 2008 Dec;93(12):4924-32
references.pmid: 18782879
references.citation: Endocrinology. 1996 Nov;137(11):4779-85
references.pmid: 8895347
references.citation: Ann N Y Acad Sci. 1998 Dec 11;865:486-91
references.pmid: 9928056
references.citation: Endocrinology. 1991 Oct;129(4):2260-2
references.pmid: 1915106
references.citation: J Biol Chem. 1995 Feb 24;270(8):4101-7
references.pmid: 7876160
references.citation: Ann N Y Acad Sci. 1996 Dec 26;805:677-83
references.pmid: 8993460
references.citation: J Biol Chem. 2003 Jun 13;278(24):22128-35
references.pmid: 12670947
references.citation: Regul Pept. 2002 Nov 15;109(1-3):75-81
references.pmid: 12409218
references.citation: Brain Res Mol Brain Res. 2000 May 31;78(1-2):59-68
references.pmid: 10891585
references.citation: Endocrinology. 2003 Jun;144(6):2409-16
references.pmid: 12746302
references.citation: Biol Reprod. 2013 Feb 14;88(2):35
references.pmid: 23197164
references.citation: Mol Endocrinol. 2004 Jan;18(1):173-83
references.pmid: 14593074
references.citation: Mol Cell Biol. 1995 Aug;15(8):4225-31
references.pmid: 7623817
references.citation: Mol Cell Biol. 2005 Nov;25(22):9829-44
references.pmid: 16260600
references.citation: Mol Cell Endocrinol. 1996 Mar 25;117(2):227-32
references.pmid: 8737384
references.citation: Exp Biol Med (Maywood). 2003 Dec;228(11):1282-90
references.pmid: 14681544
references.citation: Peptides. 2010 Sep;31(9):1748-55
references.pmid: 20553777
references.citation: Pharmacol Rev. 2000 Jun;52(2):269-324
references.pmid: 10835102
references.citation: J Mol Endocrinol. 2003 Oct;31(2):263-78
references.pmid: 14519095
references.citation: Biol Reprod. 2009 Sep;81(3):465-72
references.pmid: 19458315
references.citation: Biol Reprod. 2005 Sep;73(3):491-9
references.pmid: 15917345
references.citation: Mol Cell Endocrinol. 2001 May 15;176(1-2):135-44
references.pmid: 11369453
references.citation: J Leukoc Biol. 2004 Mar;75(3):529-40
references.pmid: 15001660
references.citation: J Mol Neurosci. 2003 Apr;20(2):141-52
references.pmid: 12794308
references.citation: J Vet Med Sci. 2000 Jul;62(7):731-6
references.pmid: 10945291
references.citation: Biochem Biophys Res Commun. 2001 May 4;283(2):412-6
references.pmid: 11327717
references.citation: Cell. 1999 May 28;97(5):587-98
references.pmid: 10367888
references.citation: J Endocrinol. 1992 Jul;134(1):33-41
references.pmid: 1380057
references.citation: Mol Endocrinol. 2007 Dec;21(12):3071-86
references.pmid: 17823303
references.citation: Mol Endocrinol. 2009 Jul;23(7):1022-32
references.pmid: 19342443
references.citation: Mol Cell Endocrinol. 2001 Jul 5;181(1-2):15-26
references.pmid: 11476937
references.citation: Mol Cell Endocrinol. 2002 Jun 28;192(1-2):55-64
references.pmid: 12088867
references.citation: Endocrinology. 1999 Nov;140(11):5185-94
references.pmid: 10537148
references.citation: Mol Endocrinol. 2008 Apr;22(4):781-98
references.pmid: 18174356
references.citation: J Biol Chem. 2001 Jun 29;276(26):23562-71
references.pmid: 11320087
references.citation: Peptides. 2008 Apr;29(4):571-7
references.pmid: 18243417
references.citation: Endocrinology. 1999 Feb;140(2):818-26
references.pmid: 9927311
references.citation: Endocr Rev. 2000 Dec;21(6):619-70
references.pmid: 11133067
references.citation: Endocrinology. 1994 Jan;134(1):315-23
references.pmid: 7903932
references.citation: Endocrinology. 2001 May;142(5):1703-9
references.pmid: 11316732
references.citation: Biol Reprod. 2007 Dec;77(6):1073-80
references.pmid: 17699734
references.citation: Peptides. 1998;19(6):1069-72
references.pmid: 9700757
references.citation: Ann N Y Acad Sci. 1996 Dec 26;805:343-52; discussion 352-4
references.pmid: 8993415
references.citation: Endocrinol Jpn. 1992 Feb;39(1):153-6
references.pmid: 1606917
references.citation: Biol Reprod. 2002 Sep;67(3):725-34
references.pmid: 12193378
references.citation: Life Sci. 1995 Feb 17;56(13):1103-11
references.pmid: 9001444
references.citation: J Mol Endocrinol. 2011 Jul 18;47(1):45-58
references.pmid: 21571865
references.citation: Mol Cell Endocrinol. 2006 Sep 26;257-258:65-74
references.pmid: 16893604
references.citation: Endocrinology. 1998 Apr;139(4):1731-7
references.pmid: 9528956
references.citation: Mol Cell Biol. 1993 Jul;13(7):3999-4010
references.pmid: 8321207
references.citation: Mol Cell Biol. 1994 Aug;14(8):5592-602
references.pmid: 7518566
references.citation: Mol Hum Reprod. 2000 Mar;6(3):238-45
references.pmid: 10694271
references.citation: Mol Endocrinol. 2001 Feb;15(2):319-37
references.pmid: 11158337
references.citation: J Biol Chem. 2002 Aug 30;277(35):32099-108
references.pmid: 12050161
references.citation: Front Neuroendocrinol. 1995 Jan;16(1):53-88
references.pmid: 7768322
references.citation: Blood. 1996 Feb 1;87(3):999-1005
references.pmid: 8562972
references.citation: J Neurochem. 2006 Aug;98(3):773-81
references.pmid: 16893419
references.citation: Exp Clin Endocrinol. 1993;101(5):290-6
references.pmid: 8299705