title: Prolactin signaling through the short isoform of the mouse prolactin receptor regulates DNA binding of specific transcription factors, often with opposite effects in different reproductive issues.
abstract: BACKGROUND
  It has been well established that prolactin (PRL) signals through the long form of its receptor (PRL-RL) and activates the Jak/Stat pathway for transcription of PRL target genes. However, signaling pathways mediated through the short PRL-R isoform (PRL-RS) remains controversial. Our recent finding that PRL signaling through PRL-RS represses two transcription factors critical for follicular development lead us to examine other putative PRL/PRL-RS target transcription factors in the decidua and ovary, two well-known target tissues of PRL action in reproduction.
  
  
  METHODS
  In this investigation we used mice expressing PRL-RS on a PRL-R knockout background and a combo protein/DNA array to study the transcription factors regulated by PRL through PRL-RS only.
  
  
  RESULTS
  We show that PRL activation of the PRL-RS receptor either stimulates or inhibits the DNA binding activity of a substantial number of transcription factors in the decidua as well as ovary. We found few transcription factors to be similarly regulated in both tissues, while most transcription factors are oppositely regulated by PRL in the decidua and ovary. In addition, some transcription factors are regulated by PRL only in the ovary or only in the decidua. Several of these transcription factors are involved in physiological pathways known to be regulated by PRL while others are novel.
  
  
  CONCLUSIONS
  Our results clearly indicate that PRL does signal through PRL-RS in the decidua as well as the ovary, independently of PRL-RL, and activates/represses transcription factors in a tissue specific manner. This is the first report showing PRL/PRL-RS regulation of specific transcription factors. Many of these transcription factors were not previously known to be PRL targets, suggesting novel physiological roles for this hormone.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Illinois 60612, USA. sangyen@uic.edu
authors.forename: Y Sangeeta
authors.initials: YS
authors.lastname: Devi
authors.forename: Aurora
authors.initials: A
authors.lastname: Shehu
authors.forename: Julia
authors.initials: J
authors.lastname: Halperin
authors.forename: Carlos
authors.initials: C
authors.lastname: Stocco
authors.forename: Jamie
authors.initials: J
authors.lastname: Le
authors.forename: Anita M
authors.initials: AM
authors.lastname: Seibold
authors.forename: Geula
authors.initials: G
authors.lastname: Gibori
mesh_terms: D000818:Animals; D000071616:CDX2 Transcription Factor; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D003656:Decidua / Q000187:drug effects* / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D051757:PAX5 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000008:administration & dosage / Q000494:pharmacology*; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000071616:CDX2 Transcription Factor; C487514:Cdx2 protein, mouse; D050676:Core Binding Factor Alpha 2 Subunit; D005136:Eye Proteins; D018398:Homeodomain Proteins; D051757:PAX5 Transcription Factor; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; C497282:Pax5 protein, mouse; C000605732:Pax6 protein, mouse; D020033:Protein Isoforms; D011981:Receptors, Prolactin; D012097:Repressor Proteins; C493726:Runx1 protein, mouse; D014157:Transcription Factors; D011388:Prolactin; D004247:DNA
references.citation: J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):449-56
references.pmid: 12943735
references.citation: J Biol Chem. 2001 Jun 8;276(23):20029-38
references.pmid: 11274169
references.citation: Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4031-5
references.pmid: 7537382
references.citation: Nat Rev Cancer. 2002 Jul;2(7):502-13
references.pmid: 12094236
references.citation: Endocrinology. 1997 Nov;138(11):4812-20
references.pmid: 9348210
references.citation: J Vasc Res. 2007;44(1):19-30
references.pmid: 17164560
references.citation: Mol Cell Endocrinol. 2005 Mar 31;232(1-2):9-19
references.pmid: 15737464
references.citation: Fertil Steril. 2009 May;91(5 Suppl):1998-2005
references.pmid: 18439600
references.citation: Mol Cell Endocrinol. 2002 Jun 28;192(1-2):45-53
references.pmid: 12088866
references.citation: Endocrinology. 1994 Sep;135(3):1272-9
references.pmid: 8070373
references.citation: Ann N Y Acad Sci. 2007 Jun;1108:157-65
references.pmid: 17893982
references.citation: Exp Biol Med (Maywood). 2003 Dec;228(11):1282-90
references.pmid: 14681544
references.citation: Hum Reprod Update. 2006 Sep-Oct;12(5):573-84
references.pmid: 16835432
references.citation: Endocr Rev. 2003 Feb;24(1):1-27
references.pmid: 12588805
references.citation: Biochem Biophys Res Commun. 2006 Jun 16;344(4):1300-7
references.pmid: 16650815
references.citation: Biol Reprod. 2004 Jan;70(1):39-45
references.pmid: 12954737
references.citation: J Mammary Gland Biol Neoplasia. 2008 Mar;13(1):69-79
references.pmid: 18219563
references.citation: Hum Reprod. 1991 Jul;6(6):791-8
references.pmid: 1757516
references.citation: Mol Endocrinol. 2006 Sep;20(9):2156-72
references.pmid: 16675540
references.citation: Nature. 2005 Dec 15;438(7070):981-7
references.pmid: 16355216
references.citation: Placenta. 2004 Apr;25 Suppl A:S26-31
references.pmid: 15033303
references.citation: Biol Reprod. 2008 Jun;78(6):1038-48
references.pmid: 18287572
references.citation: J Biol Chem. 2008 Jun 20;283(25):17003-8
references.pmid: 18434325
references.citation: Endocrinology. 2009 Jul;150(7):3327-35
references.pmid: 19342455
references.citation: Endocr Rev. 1991 Aug;12(3):235-51
references.pmid: 1935820
references.citation: J Biol Chem. 1995 May 5;270(18):10664-70
references.pmid: 7537736
references.citation: Mol Endocrinol. 2005 Sep;19(9):2299-308
references.pmid: 15890675
references.citation: Development. 1996 Feb;122(2):461-72
references.pmid: 8625797
references.citation: Mol Endocrinol. 2003 Jun;17(6):1066-74
references.pmid: 12624115
references.citation: Eur J Endocrinol. 1999 Oct;141(4):426-30
references.pmid: 10526259
references.citation: Mol Endocrinol. 1999 Feb;13(2):239-53
references.pmid: 9973254
references.citation: J Biol Chem. 2003 Nov 14;278(46):46171-8
references.pmid: 12952963
references.citation: Endocr Rev. 2008 Feb;29(1):1-41
references.pmid: 18057139
references.citation: Endocr Rev. 1998 Jun;19(3):225-68
references.pmid: 9626554
references.citation: Mol Cell Biochem. 1990 Jun 1;95(1):43-7
references.pmid: 2366751
references.citation: Biochim Biophys Acta. 1978 Apr 6;473(3-4):241-93
references.pmid: 350276
references.citation: Mol Endocrinol. 1989 Apr;3(4):674-80
references.pmid: 2725531
references.citation: Proc Soc Exp Biol Med. 1997 May;215(1):35-52
references.pmid: 9142136
references.citation: Biol Reprod. 2008 May;78(5):888-95
references.pmid: 18218610
references.citation: Endocrinology. 1996 Nov;137(11):4878-85
references.pmid: 8895360
references.citation: Mol Cell Endocrinol. 2000 Jan 25;159(1-2):171-7
references.pmid: 10687862
references.citation: EMBO J. 2003 Dec 1;22(23):6335-45
references.pmid: 14633992
references.citation: Endocrinology. 2008 Jun;149(6):3025-36
references.pmid: 18308847
references.citation: Endocrinology. 2008 Apr;149(4):1926-34
references.pmid: 18174278
references.citation: J Mol Endocrinol. 2004 Apr;32(2):365-83
references.pmid: 15072545
references.citation: Biochem Mol Biol Int. 1998 Jan;44(1):51-8
references.pmid: 9503147
references.citation: Cancer Res. 2003 Aug 1;63(15):4620-5
references.pmid: 12907641
references.citation: J Cell Physiol. 2009 Jun;219(3):626-33
references.pmid: 19170064
references.citation: Mol Cell Endocrinol. 2007 Jan 15;263(1-2):181-9
references.pmid: 17097802
references.citation: Biol Reprod. 2003 Jun;68(6):2180-8
references.pmid: 12606399
references.citation: Mol Endocrinol. 2008 Feb;22(2):513-22
references.pmid: 17975019
references.citation: Ann N Y Acad Sci. 1991;622:57-68
references.pmid: 2064208
references.citation: Endocrinology. 2009 Feb;150(2):915-28
references.pmid: 18845636
references.citation: Toxicol Appl Pharmacol. 2001 Dec 15;177(3):256-63
references.pmid: 11749125
references.citation: Mod Pathol. 2008 May;21(5):565-71
references.pmid: 18246042
references.citation: Mol Cell Endocrinol. 2001 Nov 26;184(1-2):151-61
references.pmid: 11694351
references.citation: Mol Endocrinol. 1997 Jul;11(8):1020-32
references.pmid: 9212050
references.citation: Mol Endocrinol. 1997 Sep;11(10):1449-57
references.pmid: 9280060
references.citation: Endocrinology. 2005 Jun;146(6):2807-16
references.pmid: 15731358
references.citation: Endocr Rev. 2007 Feb;28(1):117-49
references.pmid: 17077191
references.citation: Reprod Toxicol. 2000 Sep-Oct;14(5):377-84
references.pmid: 11020650
references.citation: Lancet. 1979 Oct 6;2(8145):737-8
references.pmid: 90818
references.citation: Int J Mol Med. 2002 Mar;9(3):287-92
references.pmid: 11836635
references.citation: Trends Endocrinol Metab. 2003 Apr;14(3):118-23
references.pmid: 12670737
references.citation: J Clin Endocrinol Metab. 2007 Jan;92(1):322-7
references.pmid: 17032711
references.citation: J Clin Endocrinol Metab. 2003 Jul;88(7):3415-20
references.pmid: 12843196
references.citation: Mol Hum Reprod. 1996 Mar;2(3):185-93
references.pmid: 9238678
references.citation: Endocrinology. 2009 Jul;150(7):3291-300
references.pmid: 19342459
references.citation: Nat Rev Immunol. 2009 Jan;9(1):47-56
references.pmid: 19104498
references.citation: Reprod Biol Endocrinol. 2006 Apr 12;4:21
references.pmid: 16611366
references.citation: Mol Endocrinol. 1990 Jan;4(1):13-12
references.pmid: 1970119
references.citation: J Biol Chem. 2004 Jun 4;279(23):24530-9
references.pmid: 15051730