title: Translating extranuclear steroid receptor signaling to clinical medicine.
abstract: The existence and function of extranuclear steroid receptors (SR) to rapidly modulate signal transduction is now acknowledged as present in cells and organs throughout the body. Work over the past 15 years has defined key mechanisms that are required for sex steroid receptors to traffic to the plasma membrane, but mechanisms of localization in other cell organelles such as mitochondria is still unclear. Signaling by membrane-localized SR has now been reported to impact many aspects of adult organ functions, while the roles in organ development are under investigation. In hormone-responsive cancers, both extranuclear and nuclear sex steroid receptors appear to collaborate in the regulation of some key genes that promote malignancy. Here, I review what is understood about the impact of extranuclear steroid receptor signaling to mitigate or promote disease processes.
authors.affiliation: Division of Endocrinology, Departments of Medicine, University of California, Irvine, CA, 92717, USA, ellis.levin@va.gov.
authors.forename: Ellis R
authors.initials: ER
authors.lastname: Levin
mesh_terms: D001943:Breast Neoplasms / Q000209:etiology; D006332:Cardiomegaly / Q000517:prevention & control; D047629:Estrogen Receptor beta / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000209:etiology; D011944:Receptors, Androgen / Q000502:physiology; D011960:Receptors, Estrogen / Q000502:physiology; D011987:Receptors, Steroid / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D047629:Estrogen Receptor beta; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011987:Receptors, Steroid
references.citation: EMBO Mol Med. 2012 Nov;4(11):1200-13
references.pmid: 23065768
references.citation: J Biol Chem. 2009 Feb 6;284(6):3488-95
references.pmid: 19054762
references.citation: J Appl Physiol (1985). 2012 Jul;113(1):149-58
references.pmid: 22628376
references.citation: Mol Endocrinol. 2010 Sep;24(9):1737-47
references.pmid: 20660297
references.citation: Mol Biol Cell. 2013 Dec;24(24):3805-18
references.pmid: 24152730
references.citation: Mol Endocrinol. 2012 Dec;26(12):2058-70
references.pmid: 23028062
references.citation: Mol Biol Cell. 2012 Jan;23(1):188-99
references.pmid: 22031296
references.citation: Biochim Biophys Acta. 2005 Oct 30;1746(1):1-17
references.pmid: 16169101
references.citation: Mol Endocrinol. 2005 Apr;19(4):833-42
references.pmid: 15695368
references.citation: Mol Biol Cell. 2006 May;17(5):2125-37
references.pmid: 16495339
references.citation: Cancer Res. 2004 Oct 1;64(19):7156-68
references.pmid: 15466214
references.citation: Breast. 2013 Feb;22(1):1-12
references.pmid: 23084121
references.citation: Mol Endocrinol. 2013 Apr;27(4):649-56
references.pmid: 23443267
references.citation: Oncogene. 2013 Jul 4;32(27):3274-85
references.pmid: 22907432
references.citation: Breast Cancer Res Treat. 2012 Nov;136(2):331-45
references.pmid: 23073759
references.citation: Endocrinology. 2008 Jul;149(7):3361-9
references.pmid: 18372323
references.citation: Endocrinology. 2013 Feb;154(2):819-30
references.pmid: 23183182
references.citation: Mol Med. 2013 Aug 28;19:253-62
references.pmid: 23821363
references.citation: Neurobiol Dis. 2013 Oct;58:209-19
references.pmid: 23774254
references.citation: Mol Endocrinol. 2010 May;24(5):993-1006
references.pmid: 20351197
references.citation: Endocrinology. 2011 Dec;152(12):4489-95
references.pmid: 22028449
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 15;107(24):11122-7
references.pmid: 20534466
references.citation: Oncogene. 1999 Nov 4;18(46):6322-9
references.pmid: 10597231
references.citation: J Clin Invest. 2010 Jul;120(7):2319-30
references.pmid: 20577047
references.citation: Circulation. 2007 Jun 26;115(25):3197-204
references.pmid: 17562954
references.citation: Annu Rev Med. 2011;62:233-47
references.pmid: 20887199
references.citation: Mol Biol Cell. 2009 Jul;20(14):3374-89
references.pmid: 19477925
references.citation: Mol Biol Cell. 2002 Oct;13(10):3720-9
references.pmid: 12388769
references.citation: Am J Physiol Endocrinol Metab. 2004 Jun;286(6):E1011-22
references.pmid: 14736707
references.citation: J Biol Chem. 2003 Jan 24;278(4):2701-12
references.pmid: 12421825
references.citation: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4130-5
references.pmid: 15024130
references.citation: JAMA. 2003 Jun 25;289(24):3243-53
references.pmid: 12824205
references.citation: Transl Stroke Res. 2013 Aug;4(4):390-401
references.pmid: 24323337
references.citation: J Clin Invest. 2012 Jul;122(7):2469-81
references.pmid: 22684108
references.citation: Cardiovasc Res. 2008 Mar 1;77(4):774-81
references.pmid: 18056768
references.citation: Steroids. 2011 Aug;76(9):822-8
references.pmid: 21354434
references.citation: Mol Endocrinol. 2005 Feb;19(2):327-39
references.pmid: 15486045
references.citation: Nature. 2008 Dec 4;456(7222):663-6
references.pmid: 19005469
references.citation: Mol Cell. 2006 Nov 3;24(3):367-81
references.pmid: 17081988
references.citation: J Clin Invest. 2003 Jun;111(11):1651-64
references.pmid: 12782668
references.citation: Oncogene. 2012 May 31;31(22):2703-14
references.pmid: 21963847
references.citation: Mol Cell Biol. 2007 Jan;27(2):466-80
references.pmid: 17074804
references.citation: Mol Cell Biol. 2004 Jul;24(13):5900-13
references.pmid: 15199145
references.citation: Biomaterials. 2013 Dec;34(38):10228-37
references.pmid: 24055523
references.citation: Science. 2002 Oct 25;298(5594):843-6
references.pmid: 12399595
references.citation: J Biol Chem. 2010 Sep 10;285(37):28787-95
references.pmid: 20628053
references.citation: EMBO J. 1996 Mar 15;15(6):1292-300
references.pmid: 8635462
references.citation: Am J Physiol Heart Circ Physiol. 2003 May;284(5):H1560-9
references.pmid: 12560213
references.citation: Endocrinology. 2007 Aug;148(8):4091-101
references.pmid: 17525128
references.citation: Oncogene. 2014 Mar 20;33(12):1570-80
references.pmid: 23604116
references.citation: Mol Endocrinol. 2010 Nov;24(11):2152-65
references.pmid: 20810711
references.citation: Mol Endocrinol. 2014 Apr;28(4):442-57
references.pmid: 24606123
references.citation: Endocrinology. 2013 Nov;154(11):4352-64
references.pmid: 23970786
references.citation: Annu Rev Pharmacol Toxicol. 2007;47:657-80
references.pmid: 16918306
references.citation: Sci Signal. 2013 May 21;6(276):ra36
references.pmid: 23695162