title: The luteinizing hormone receptor: insights into structure-function relationships and hormone-receptor-mediated changes in gene expression in ovarian cancer cells.
abstract: The luteinizing hormone receptor (LHR), one of the three glycoprotein hormone receptors, is necessary for critical reproductive processes, including gonadal steroidogenesis, oocyte maturation and ovulation, and male sex differentiation. Moreover, it has been postulated to contribute to certain neoplasms, particularly ovarian cancer. A member of the G protein-coupled receptor family, LHR contains a relatively large extracellular domain responsible for high affinity hormone binding; transmembrane activation then leads to G protein coupling and subsequent second messenger production. This review deals with recent advances in our understanding of LHR structure and structure-function relationships, as well as hormone-mediated changes in gene expression in ovarian cancer cells expressing LHR. Suggestions are also made for critical gaps that need to be filled as the field advances, including determination of the three-dimensional structure of inactive and active receptor, elucidation of the mechanism by which hormone binding to the extracellular domain triggers the activation of Gs, clarification of the putative roles of LHR in non-gonadal tissues, and the role, if any, of activated receptor in the development or progression of ovarian cancer.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Georgia, Athens, GA 30602, USA. puett@bmb.uga.edu
authors.forename: David
authors.initials: D
authors.lastname: Puett
authors.forename: Krassimira
authors.initials: K
authors.lastname: Angelova
authors.forename: Marcelo Rocha
authors.initials: MR
authors.lastname: da Costa
authors.forename: Susanne W
authors.initials: SW
authors.lastname: Warrenfeltz
authors.forename: Francesca
authors.initials: F
authors.lastname: Fanelli
mesh_terms: D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D010051:Ovarian Neoplasms / Q000235:genetics*; D011974:Receptors, LH / Q000737:chemistry / Q000502:physiology*
chemical_list: D006728:Hormones; D011974:Receptors, LH; D019204:GTP-Binding Proteins
references.citation: Neuron. 2003 Apr 24;38(2):177-85
references.pmid: 12718853
references.citation: Science. 2002 Aug 16;297(5584):1176-9
references.pmid: 12183630
references.citation: Mol Endocrinol. 2006 Sep;20(9):2247-55
references.pmid: 16543405
references.citation: Fertil Steril. 2002 Nov;78(5):1096-9
references.pmid: 12414000
references.citation: J Mol Endocrinol. 2003 Aug;31(1):157-68
references.pmid: 12914533
references.citation: EMBO J. 2005 Jun 1;24(11):1954-64
references.pmid: 15889138
references.citation: Mol Cell Endocrinol. 2001 Feb 14;172(1-2):213-22
references.pmid: 11165055
references.citation: J Biol Chem. 2003 May 2;278(18):15505-13
references.pmid: 12598521
references.citation: Structure. 1994 Jun 15;2(6):545-58
references.pmid: 7922031
references.citation: Prog Mol Biol Transl Sci. 2009;89:97-114
references.pmid: 20374734
references.citation: J Biol Chem. 2001 Feb 2;276(5):3451-8
references.pmid: 10964934
references.citation: J Mol Biol. 1993 Dec 5;234(3):779-815
references.pmid: 8254673
references.citation: Endocrinology. 2000 Dec;141(12):4518-23
references.pmid: 11108263
references.citation: Cancer Res. 1993 Feb 15;53(4):891-8
references.pmid: 8094034
references.citation: Mol Endocrinol. 2007 Feb;21(2):574-80
references.pmid: 17110401
references.citation: Exp Cell Res. 2003 Mar 10;284(1):99-110
references.pmid: 12648469
references.citation: Mol Endocrinol. 2002 Dec;16(12):2733-45
references.pmid: 12456794
references.citation: Glia. 2005 Jan 1;49(1):24-35
references.pmid: 15390106
references.citation: Gynecol Oncol. 2000 Jan;76(1):80-8
references.pmid: 10620446
references.citation: Eur J Biochem. 1999 Mar;260(2):490-8
references.pmid: 10095786
references.citation: Cell Mol Life Sci. 2008 Aug;65(16):2484-92
references.pmid: 18438608
references.citation: Reproduction. 2005 Sep;130(3):263-74
references.pmid: 16123233
references.citation: J Mol Biol. 1999 Jun 25;289(5):1375-85
references.pmid: 10373373
references.citation: J Biol Chem. 2001 Feb 2;276(5):3426-35
references.pmid: 10880516
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:59-64
references.pmid: 17052834
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:144-52
references.pmid: 17055148
references.citation: Trends Biochem Sci. 2004 Mar;29(3):119-26
references.pmid: 15003269
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:126-36
references.pmid: 17059864
references.citation: J Biol Chem. 2007 Aug 31;282(35):25527-39
references.pmid: 17609213
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:137-43
references.pmid: 17055146
references.citation: Endocrinology. 2003 Jan;144(1):129-37
references.pmid: 12488338
references.citation: Mol Endocrinol. 2003 Jul;17(7):1192-202
references.pmid: 12677007
references.citation: J Biol Chem. 2001 Feb 2;276(5):3436-42
references.pmid: 10884391
references.citation: J Biol Chem. 2002 Aug 30;277(35):32202-13
references.pmid: 12070159
references.citation: J Biol Chem. 2002 May 3;277(18):15795-800
references.pmid: 11859079
references.citation: Thyroid. 2007 May;17(5):395-410
references.pmid: 17542669
references.citation: Methods Enzymol. 2003;374:461-91
references.pmid: 14696385
references.citation: Mol Cell Endocrinol. 2007 Apr 15;269(1-2):61-4
references.pmid: 17353087
references.citation: Methods. 2000 May;21(1):59-66
references.pmid: 10764607
references.citation: Mol Endocrinol. 2002 Jun;16(6):1299-308
references.pmid: 12040016
references.citation: Endocr Rev. 2007 Jun;28(4):440-61
references.pmid: 17463396
references.citation: Mol Cancer Res. 2008 Nov;6(11):1775-85
references.pmid: 19010824
references.citation: Nature. 1994 Mar 17;368(6468):251-5
references.pmid: 8145825
references.citation: Endocr Rev. 2002 Apr;23(2):141-74
references.pmid: 11943741
references.citation: Mol Cell Endocrinol. 2009 Jan 27;298(1-2):33-41
references.pmid: 19013498
references.citation: Mol Endocrinol. 1996 Sep;10(9):1147-59
references.pmid: 8885249
references.citation: J Biol Chem. 1996 Dec 6;271(49):31638-42
references.pmid: 8940183
references.citation: J Mol Biol. 1997 Sep 12;272(1):106-20
references.pmid: 9299341
references.citation: Nature. 1994 Jun 9;369(6480):455-61
references.pmid: 8202136
references.citation: Int J Cancer. 2000 Jun 1;86(5):644-51
references.pmid: 10797285
references.citation: J Biol Chem. 2004 Jun 11;279(24):25503-10
references.pmid: 15044447
references.citation: Mol Endocrinol. 2006 Aug;20(8):1880-93
references.pmid: 16574743
references.citation: Hum Reprod Update. 2007 Mar-Apr;13(2):143-62
references.pmid: 17071638
references.citation: Mol Pharmacol. 2009 Jan;75(1):1-12
references.pmid: 18945819
references.citation: Ann N Y Acad Sci. 2005 Dec;1061:41-54
references.pmid: 16467256
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:73-82
references.pmid: 17045735
references.citation: Mol Cell Endocrinol. 2007 Jan 2;260-262:294-300
references.pmid: 17045736
references.citation: Endocr Rev. 2009 Apr;30(2):133-51
references.pmid: 19176466
references.citation: Nature. 2005 Jan 20;433(7023):269-77
references.pmid: 15662415
references.citation: Nature. 2009 May 21;459(7245):356-63
references.pmid: 19458711
references.citation: Curr Protein Pept Sci. 2009 Apr;10(2):173-85
references.pmid: 19355984
references.citation: J Mol Endocrinol. 2005 Apr;34(2):489-503
references.pmid: 15821112
references.citation: Eur J Biochem. 1996 Oct 1;241(1):229-42
references.pmid: 8898911
references.citation: Cancer Res. 2006 Apr 1;66(7):3912-20
references.pmid: 16585220
references.citation: J Biol Chem. 2008 Sep 19;283(38):25821-8
references.pmid: 18641392
references.citation: Biol Reprod. 1998 Jun;58(6):1337-42
references.pmid: 9623590
references.citation: J Biol Chem. 2004 Feb 13;279(7):5904-14
references.pmid: 14594799
references.citation: Mol Endocrinol. 2008 Jan;22(1):126-38
references.pmid: 17872379
references.citation: Mol Endocrinol. 2001 Mar;15(3):378-89
references.pmid: 11222739
references.citation: Mol Endocrinol. 2003 Oct;17(10):1972-81
references.pmid: 12869592
references.citation: Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2319-24
references.pmid: 20080658
references.citation: J Biol Chem. 2009 Mar 20;284(12):7483-94
references.pmid: 19147490
references.citation: EMBO J. 2003 Jun 2;22(11):2692-703
references.pmid: 12773385
references.citation: Cell Signal. 2009 Nov;21(11):1663-71
references.pmid: 19616090
references.citation: Endocrinology. 2008 Apr;149(4):1705-17
references.pmid: 18162522
references.citation: Endocrinology. 1999 Oct;140(10):4558-63
references.pmid: 10499511