title: Expression and dexamethasone-induced nuclear translocation of glucocorticoid and mineralocorticoid receptors in guinea pig cochlear cells.
abstract: Glucocorticoids (GC) are powerful anti-inflammatory agents frequently used to protect the auditory organ against damage associated with a variety of conditions, including noise exposure and ototoxic drugs as well as bacterial and viral infections. In addition to glucocorticoid receptors (GC-R), natural and synthetic GC are known to bind mineralocorticoid receptors (MC-R) with great affinity. We used light and laser scanning confocal microscopy to investigate the expression of GC-R and MC-R in different cell populations of the guinea pig cochlea, and their translocation to different cell compartments after treatment with the synthetic GC dexamethasone. We found expression of both types of receptors in the cytoplasm and nucleus of sensory inner and outer hair cells as well as pillar, Hensen and Deiters cells in the organ of Corti, inner and outer sulcus cells, spiral ganglion neurons and several types of spiral ligament and spiral limbus cells; stria vascularis cells expressed mostly MC-R whereas fibrocytes type IV were positive for GC-R only. GC-R and MC-R were also localized at or near the plasma membrane of pillar cells and outer hair cells, whereas GC-R were found at or near the plasma membrane of Hensen cells only. We investigated the relative levels of receptor expression in the cytoplasm and the nucleus of Hensen cells treated with dexamethasone, and found they varied in a way suggestive of dose-induced translocation. These results suggest that the oto-protective effects of GC could be associated with the concerted activation of genomic and non-genomic, GC-R and MC-R mediated signaling pathways in different regions of the cochlea.
authors: Division of Cell Biology and Genetics, House Research Institute, Los Angeles, CA 90057, USA.
authors: Sung-Hee
authors: SH
authors: Kil
authors: Federico
authors: F
authors: Kalinec
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D002478:Cells, Cultured; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005455:Fluorescent Antibody Technique; D006168:Guinea Pigs; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D020011:Protective Agents / Q000494:pharmacology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000187:drug effects* / Q000378:metabolism
chemical_list: D020011:Protective Agents; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D003907:Dexamethasone
references: Am J Physiol. 1994 Aug;267(2 Pt 1):E268-72
references: 8074206
references: Hear Res. 1993 Sep;69(1-2):10-4
references: 8226329
references: J Neurosci Res. 2006 Mar;83(4):575-83
references: 16429448
references: Endocrinology. 1985 Dec;117(6):2505-11
references: 2998738
references: J Neurosci. 1996 May 15;16(10):3534-40
references: 8627386
references: FASEB J. 2004 Jan;18(1):70-80
references: 14718388
references: Science. 1993 Feb 19;259(5098):1161-5
references: 8382376
references: Annu Rev Pharmacol Toxicol. 2003;43:175-97
references: 12195028
references: Brain Res Brain Res Rev. 1997 Jun;24(1):1-27
references: 9233540
references: J Steroid Biochem Mol Biol. 2003 Jun;85(2-5):375-81
references: 12943725
references: Biochem Biophys Res Commun. 2005 Oct 7;335(4):1002-7
references: 16111661
references: Mol Cell. 2000 May;5(5):831-40
references: 10882119
references: Hear Res. 1995 Jul;87(1-2):220-7
references: 8567439
references: Mol Endocrinol. 2005 Sep;19(9):2211-21
references: 15802372
references: Synapse. 2009 Sep;63(9):745-51
references: 19484722
references: Hear Res. 1997 Mar;105(1-2):57-64
references: 9083804
references: Eur J Pharmacol. 1993 Oct 15;247(2):145-54
references: 8282004
references: Hippocampus. 1992 Oct;2(4):421-30
references: 1308198
references: Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):9191-6
references: 22619324
references: Biochem Biophys Res Commun. 1998 Mar 17;244(2):403-7
references: 9514937
references: Neuroscience. 2005;136(1):289-99
references: 16181741
references: Laryngoscope. 1999 Apr;109(4):626-30
references: 10201753
references: Biol Psychiatry. 2010 Jul 15;68(2):197-204
references: 20385375
references: Science. 1987 Jul 17;237(4812):268-75
references: 3037703
references: Hear Res. 1994 Aug;78(2):175-80
references: 7982810
references: J Neurosci Res. 1993 May 1;35(1):14-9
references: 8510182
references: Neuroendocrinology. 1992 Mar;55(3):344-50
references: 1323803
references: Hear Res. 2006 Dec;222(1-2):115-24
references: 17081714
references: Acta Otolaryngol. 2001 Oct;121(7):794-802
references: 11718241
references: Hear Res. 2011 Jul;277(1-2):4-19
references: 21329750
references: Acta Otolaryngol. 1996 May;116(3):493-6
references: 8790754
references: J Med Chem. 1993 Aug 6;36(16):2404-7
references: 8360885
references: J Assoc Res Otolaryngol. 2003 Sep;4(3):339-52
references: 14690052
references: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):19204-7
references: 16361444
references: Nat Rev Mol Cell Biol. 2003 Jan;4(1):46-56
references: 12511868
references: Funct Neurol. 1995 Jul-Oct;10(4-5):183-94
references: 8749045
references: Hear Res. 1989 Sep;41(2-3):217-21
references: 2530200
references: Hear Res. 2011 Nov;281(1-2):47-55
references: 21718769
references: Audiol Neurootol. 2003 Jul-Aug;8(4):177-89
references: 12811000
references: Adv Pharmacol. 2000;47:1-21
references: 10582083
references: Hear Res. 1999 Nov;137(1-2):160-6
references: 10545643
references: Hear Res. 1991 Nov;56(1-2):53-64
references: 1663106
references: J Biol Chem. 2007 Aug 3;282(31):22278-88
references: 17535799
references: Ann Otol Rhinol Laryngol. 2002 Dec;111(12 Pt 1):1133-8
references: 12498377
references: Br J Pharmacol. 2007 Dec;152(7):1012-20
references: 17906689
references: Eur J Pharmacol. 2008 Apr 7;583(2-3):312-21
references: 18275953
references: Acta Otorrinolaringol Esp. 2008 Dec;59(10):494-9
references: 19080786
references: Otolaryngol Head Neck Surg. 1999 Oct;121(4):452-6
references: 10504603
references: Hear Res. 1999 Nov;137(1-2):155-9
references: 10545642
references: Sci STKE. 2002 Jun 25;2002(138):re9
references: 12084906
references: J Cell Sci. 1996 Apr;109 ( Pt 4):787-92
references: 8718670
references: FASEB J. 1993 Oct;7(13):1283-92
references: 8405814
references: Hear Res. 1994 Jun 15;77(1-2):216-20
references: 7928734
references: Br J Pharmacol. 2009 Dec;158(7):1820-34
references: 19912231
references: Nonlinearity Biol Toxicol Med. 2005 Jan;3(1):23-56
references: 19330155
references: Hear Res. 1999 Nov;137(1-2):167-73
references: 10545644
references: Neurobiol Dis. 2007 Jan;25(1):189-97
references: 17056263
references: Acta Otolaryngol. 1996 Sep;116(5):721-5
references: 8908249
references: Am J Physiol Renal Physiol. 2004 Jun;286(6):F1127-35
references: 14996671
references: Hear Res. 2001 May;155(1-2):9-20
references: 11335072
references: Steroids. 2005 May-Jun;70(5-7):407-17
references: 15862824
references: Brain Res Mol Brain Res. 2003 Dec 12;120(1):65-72
references: 14667579
references: Br J Pharmacol. 1988 Aug;94(4):987-1015
references: 2974738
references: Neurosci Res. 1995 Dec;24(1):1-46
references: 8848287
references: PLoS One. 2010 Dec 15;5(12):e14344
references: 21179518
references: Hear Res. 1992 Jul;60(2):199-204
references: 1639729
references: Otolaryngol Head Neck Surg. 1996 Jul;115(1):38-41
references: 8758627
references: J Neurosci Methods. 2009 Jan 30;176(2):144-51
references: 18835298
references: Neuroreport. 2006 Jun 26;17(9):879-82
references: 16738480
references: News Physiol Sci. 2003 Apr;18:60-4
references: 12644621
references: J Neurosci Res. 2006 May 1;83(6):1066-76
references: 16493680
references: Proc Natl Acad Sci U S A. 1983 Oct;80(19):6056-60
references: 6310613
references: J Assoc Res Otolaryngol. 2003 Jun;4(2):176-95
references: 12943372
references: Acta Otolaryngol. 1995 Sep;115(5):643-7
references: 8928636
references: Acta Otolaryngol. 1993 Mar;113(2):160-5
references: 8475729
references: Laryngoscope. 1993 Aug;103(8):865-71
references: 8361289
references: Neuroendocrinology. 1991;53 Suppl 1:25-30
references: 1901388
references: Hear Res. 2006 Feb;212(1-2):22-32
references: 16307853
references: Trends Pharmacol Sci. 2006 May;27(5):244-50
references: 16584791
references: Front Neuroendocrinol. 2008 May;29(2):273-91
references: 18054070
references: J Bone Miner Res. 2001 Aug;16(8):1496-504
references: 11499872
references: Brain Res Brain Res Rev. 2000 Apr;32(1):163-6
references: 10751665
references: Endocrinology. 1989 Feb;124(2):687-91
references: 2912696
references: Steroids. 2008 Oct;73(9-10):1025-9
references: 18221974