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Journal of the Association for Research in Otolaryngology

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01-08-2018 | Research Article

Mechanism Underlying the Effects of Estrogen Deficiency on Otoconia

Authors: Liping Yang, Yinfang Xu, Yan Zhang, Sarath Vijayakumar, Sherri M. Jones, Yunxia (Yesha) Wang Lundberg

Published in: Journal of the Association for Research in Otolaryngology | Issue 4/2018

Abstract

Otoconia-related vertigo and balance deficits, particularly benign paroxysmal positional vertigo (BPPV), are common. Our recent studies in humans show that, while BPPV prevalence greatly increases with age in both genders, peri-menopausal women are especially susceptible. In the present study, we show that bilateral ovariectomized (OVX) mice have significant balance behavioral deficits, and that estrogen deficiency compromises otoconia maintenance and anchoring by reducing the expression of otoconial component and anchoring proteins. There is ectopic debris formation in the ampulla under estrogen deficiency due to aberrant matrix protein expression. Furthermore, phytoestrogen is effective in rescuing the otoconia abnormalities. By comparing the expression levels of known estrogen receptor (Esr) subtypes, and by examining the otoconia phenotypes of null mice for selected receptors, we postulate that Esr2 may be critical in mediating the effects of estrogen in otoconia maintenance.

Alexander A, Irving AJ, Harvey J (2017) Emerging roles for the novel estrogen-sensing receptor GPER1 in the CNS. Neuropharmacology 113:652–660CrossRefPubMed

Anniko M, Ylikoski J, Wroblewski R (1984) Microprobe analysis of human otoconia. Acta Otolaryngol 97:283–289CrossRefPubMed

Charitidi K, Meltser I, Tahera Y, Canlon B (2009) Functional responses of estrogen receptors in the male and female auditory system. Hear Res 252:71–78CrossRefPubMed

Chen J, Nathans J (2007) Estrogen-related receptor beta/NR3B2 controls epithelial cell fate and endolymph production by the stria vascularis. Dev Cell 13:325–337CrossRefPubMed

Collin RW, Kalay E, Tariq M, Peters T, van der Zwaag B, Venselaar H, Oostrik J, Lee K, Ahmed ZM, Caylan R, Li Y, Spierenburg HA, Eyupoglu E, Heister A, Riazuddin S, Bahat E, Ansar M, Arslan S, Wollnik B, Brunner HG, Cremers CW, Karaguzel A, Ahmad W, Cremers FP, Vriend G, Friedman TB, Riazuddin S, Leal SM, Kremer H (2008) Mutations of ESRRB encoding estrogen-related receptor beta cause autosomal-recessive nonsyndromic hearing impairment DFNB35. Am J Hum Genet 82:125–138CrossRefPubMedPubMedCentral

El-Mansoury M, Barrenas ML, Bryman I, Hanson C, Landin-Wilhelmsen K (2009) Impaired body balance, fine motor function and hearing in women with turner syndrome. Clin Endocrinol 71:273–278CrossRef

Fitzpatrick LA, Turner RT, Ritman ER (2003) Endochondral bone formation in the heart: a possible mechanism of coronary calcification. Endocrinology 144:2214–2219CrossRefPubMed

Ford J, Hajibeigi A, Long M, Hahner L, Gore C, Hsieh JT, Clegg D, Zerwekh J, Oz OK (2011) GPR30 deficiency causes increased bone mass, mineralization, and growth plate proliferative activity in male mice. J Bone Miner Res 26:298–307CrossRefPubMed

Gananca FF, Gazzola JM, Gananca CF, Caovilla HH, Gananca MM, Cruz OL (2010) Elderly falls associated with benign paroxysmal positional vertigo. Braz J Otorhinolaryngol 76:113–120CrossRefPubMed

Hallworth R, Wiederhold ML, Campbell JB, Steyger PS (1995) Atomic force microscope observations of otoconia in the newt. Hear Res 85:115–121CrossRefPubMed

Hawkins RD, Bashiardes S, Powder KE, Sajan SA, Bhonagiri V, Alvarado DM, Speck J, Warchol ME, Lovett M (2007) Large scale gene expression profiles of regenerating inner ear sensory epithelia. PLoS One 2:e525CrossRefPubMedPubMedCentral

Heine PA, Taylor JA, Iwamoto GA, Lubahn DB, Cooke PS (2000) Increased adipose tissue in male and female estrogen receptor-alpha knockout mice. Proc Natl Acad Sci U S A 97:12729–12734CrossRefPubMedPubMedCentral

Hess RA, Bunick D, Lubahn DB, Zhou Q, Bouma J (2000) Morphologic changes in efferent ductules and epididymis in estrogen receptor-alpha knockout mice. J Androl 21:107–121PubMed

Igarashi M, Saito R, Mizukoshi K, Alford BR (1993) Otoconia in young and elderly persons: a temporal bone study. Acta Otolaryngol Suppl 504:26–29CrossRefPubMed

Jang YS, Hwang CH, Shin JY, Bae WY, Kim LS (2006) Age-related changes on the morphology of the otoconia. Laryngoscope 116:996–1001CrossRefPubMed

Jones TA, Jones SM (1999) Short latency compound action potentials from mammalian gravity receptor organs. Hear Res 136:75–85

Jones SM, Erway LC, Bergstrom RA, Schimenti JC, Jones TA (1999) Vestibular responses to linear acceleration are absent in otoconia-deficient C57BL/6JEi-het mice. Hear Res 135:56–60CrossRefPubMed

Jones SM, Erway LC, Johnson KR, Yu H, Jones TA (2004) Gravity receptor function in mice with graded otoconial deficiencies. Hear Res 191:34–40CrossRefPubMed

Jonsson R, Sixt E, Landahl S, Rosenhall U (2004) Prevalence of dizziness and vertigo in an urban elderly population. J Vestib Res 14:47–52PubMed

Kilicdag EB, Yavuz H, Bagis T, Tarim E, Erkan AN, Kazanci F (2004) Effects of estrogen therapy on hearing in postmenopausal women. Am J Obstet Gynecol 190:77–82CrossRefPubMed

Kim MJ, Kim TH, Lee HH (2015) G-protein coupled estrogen receptor (GPER/GPR30) and Women's health. J Menopausal Med 21:79–81CrossRefPubMedPubMedCentral

Lee JH, Marcus DC (2001) Estrogen acutely inhibits ion transport by isolated stria vascularis. Hear Res 158:123–130CrossRefPubMed

Legan PK, Lukashkina VA, Goodyear RJ, Kossi M, Russell IJ, Richardson GP (2000) A targeted deletion in alpha-tectorin reveals that the tectorial membrane is required for the gain and timing of cochlear feedback. Neuron 28:273–285CrossRefPubMed

Lim DJ (1984) Otoconia in health and disease. A review Ann Otol Rhinol Laryngol Suppl 112:17–24CrossRefPubMed

Lundberg YW, Xu Y, Thiessen KD, Kramer KL (2015) Mechanisms of otoconia and otolith development. Dev Dyn 244:239–253CrossRefPubMed

Meltser I, Tahera Y, Simpson E, Hultcrantz M, Charitidi K, Gustafsson JA, Canlon B (2008) Estrogen receptor beta protects against acoustic trauma in mice. J Clin Invest 118:1563–1570CrossRefPubMedPubMedCentral

Motohashi R, Takumida M, Shimizu A, Konomi U, Fujita K, Hirakawa K, Suzuki M, Anniko M (2010) Effects of age and sex on the expression of estrogen receptor alpha and beta in the mouse inner ear. Acta Otolaryngol 130:204–214CrossRefPubMed

Murayama E, Herbomel P, Kawakami A, Takeda H, Nagasawa H (2005) Otolith matrix proteins OMP-1 and Otolin-1 are necessary for normal otolith growth and their correct anchoring onto the sensory maculae. Mech Dev 122:791–803CrossRefPubMed

Ogun OA, Buki B, Cohn ES, Janky KL, Lundberg YW (2014) Menopause and benign paroxysmal positional vertigo. Menopause 21:886–889CrossRefPubMedPubMedCentral

Ojala M, Palo J (1991) The aetiology of dizziness and how to examine a dizzy patient. Ann Med 23:225–230CrossRefPubMed

Otto C, Rohde-Schulz B, Schwarz G, Fuchs I, Klewer M, Brittain D, Langer G, Bader B, Prelle K, Nubbemeyer R, Fritzemeier KH (2008) G protein-coupled receptor 30 localizes to the endoplasmic reticulum and is not activated by estradiol. Endocrinology 149:4846–4856CrossRefPubMed

Otto C, Fuchs I, Kauselmann G, Kern H, Zevnik B, Andreasen P, Schwarz G, Altmann H, Klewer M, Schoor M, Vonk R, Fritzemeier KH (2009) GPR30 does not mediate estrogenic responses in reproductive organs in mice. Biol Reprod 80:34–41CrossRefPubMed

Pedram A, Razandi M, Levin ER (2006) Nature of functional estrogen receptors at the plasma membrane. Mol Endocrinol 20:1996–2009CrossRefPubMed

Pelekanou V, Leclercq G (2011) Recent insights into the effect of natural and environmental estrogens on mammary development and carcinogenesis. Int J Dev Biol 55:869–878CrossRefPubMed

Prossnitz ER, Maggiolini M (2009) Mechanisms of estrogen signaling and gene expression via GPR30. Mol Cell Endocrinol 308:32–38CrossRefPubMedPubMedCentral

Rajamannan NM, Gersh B, Bonow RO (2003) Calcific aortic stenosis: from bench to the bedside—emerging clinical and cellular concepts. Heart 89:801–805CrossRefPubMedPubMedCentral

Ross MD, Peacor D, Johnsson LG, Allard LF (1976) Observations on normal and degenerating human otoconia. Ann Otol Rhinol Laryngol 85:310–326CrossRefPubMed

Sajan SA, Warchol ME, Lovett M (2007) Toward a systems biology of mouse inner ear organogenesis: gene expression pathways, patterns and network analysis. Genetics 177:631–653CrossRefPubMedPubMedCentral

Simonoska R, Stenberg A, Masironi B, Sahlin L, Hultcrantz M (2009a) Estrogen receptors in the inner ear during different stages of pregnancy and development in the rat. Acta Otolaryngol 129:1175–1181CrossRefPubMed

Simonoska R, Stenberg AE, Duan M, Yakimchuk K, Fridberger A, Sahlin L, Gustafsson JA, Hultcrantz M (2009b) Inner ear pathology and loss of hearing in estrogen receptor-beta deficient mice. J Endocrinol 201:397–406CrossRefPubMed

Stein RA, McDonnell DP (2006) Estrogen-related receptor alpha as a therapeutic target in cancer. Endocr Relat Cancer 13(Suppl 1):S25–S32CrossRefPubMed

Stenberg AE, Wang H, Sahlin L, Stierna P, Enmark E, Hultcrantz M (2002) Estrogen receptors alpha and beta in the inner ear of the ‘Turner mouse’ and an estrogen receptor beta knockout mouse. Hear Res 166:1–8CrossRefPubMed

Takumida M, Zhang DM (1997) Electron probe X-ray microanalysis of otoconia in guinea pig inner ear: a comparison between young and old animals. Acta Otolaryngol 117:529–537CrossRefPubMed

Vanacker JM, Pettersson K, Gustafsson JA, Laudet V (1999) Transcriptional targets shared by estrogen receptor- related receptors (ERRs) and estrogen receptor (ER) alpha, but not by ERbeta. EMBO J 18:4270–4279CrossRefPubMedPubMedCentral

Vibert D, Sans A, Kompis M, Travo C, Muhlbauer RC, Tschudi I, Boukhaddaoui H, Hausler R (2008) Ultrastructural changes in otoconia of osteoporotic rats. Audiol Neurootol 13:293–301CrossRefPubMed

Vijayakumar S, Depreux FF, Jodelka FM, Lentz JJ, Rigo F, Jones TA, Hastings ML (2017) Rescue of peripheral vestibular function in Usher syndrome mice using a splice-switching antisense oligonucleotide. Hum Mol Genet 26:3482–3494CrossRefPubMedPubMedCentral

von Brevern M, Radtke A, Lezius F, Feldmann M, Ziese T, Lempert T, Neuhauser H (2007) Epidemiology of benign paroxysmal positional vertigo: a population based study. J Neurol Neurosurg Psychiatry 78:710–715CrossRef

von Brevern M, Bertholon P, Brandt T, Fife T, Imai T, Nuti D, Newman-Toker D (2015) Benign paroxysmal positional vertigo: diagnostic criteria. J Vestib Res 25:105–117CrossRef

Xu Y, Zhang H, Yang H, Zhao X, Lovas S, Lundberg YW (2010) Expression, functional and structural analysis of proteins critical for otoconia development. Dev Dyn 239:2659–2673CrossRefPubMedPubMedCentral

Yang H, Zhao X, Xu Y, Wang L, He Q, Lundberg YW (2011) Matrix recruitment and calcium sequestration for spatial specific otoconia development. PLoS One 6:e20498CrossRefPubMedPubMedCentral

Zhao X, Yang H, Yamoah EN, Lundberg YW (2007) Gene targeting reveals the role of Oc90 as the essential organizer of the otoconial organic matrix. Dev Biol 304:508–524CrossRefPubMedPubMedCentral

Title: Mechanism Underlying the Effects of Estrogen Deficiency on Otoconia
Authors: Liping Yang
Yinfang Xu
Yan Zhang
Sarath Vijayakumar
Sherri M. Jones
Yunxia (Yesha) Wang Lundberg
Publication date: 01-08-2018
Publisher: Springer US
Published in: Journal of the Association for Research in Otolaryngology / Issue 4/2018
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI: https://doi.org/10.1007/s10162-018-0666-8

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Mechanism Underlying the Effects of Estrogen Deficiency on Otoconia

Abstract

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