title: Estrogen receptor beta protects against acoustic trauma in mice.
abstract: The hormone estradiol affects the auditory system both by itself and by its interaction with neuroprotective factors. In this study, we examined the role of estrogen receptors (ERs) in response to auditory trauma. We found a ligand-dependent protective role for ERbeta in the auditory system by investigating mice deficient in ERalpha (ERKO mice), ERbeta (BERKO mice), and aromatase (ARKO mice). Basal auditory brainstem response (ABR) thresholds were similar in all animals. An acoustic trauma causing a temporary hearing loss raised ABR thresholds in male and female BERKO and ARKO mice compared with WT and ERKO mice. The ERalpha-selective agonist, propyl(1H) pyrazole-1,3,5-triyl-trisphenol (PPT), partially protected ARKO mice from trauma, while the ERbeta-selective agonist, 2,3-bis (4-hydroxyphenyl)-propionitrile (DPN), protected WT and ARKO mice. Immunohistochemistry and western blotting confirmed the expression of ERbeta in cochlea of WT males and females. Levels of brain-derived neurotrophic factor (BDNF), a neuroprotective peptide that can be induced by estrogen, was lower in BERKO and ARKO mice compared with WT. DPN treatment increased BDNF expression in ARKO mice. These data indicate ERbeta-mediated neuroprotection involving BDNF in the auditory system of males and females.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Inna
authors.initials: I
authors.lastname: Meltser
authors.forename: Yeasmin
authors.initials: Y
authors.lastname: Tahera
authors.forename: Evan
authors.initials: E
authors.lastname: Simpson
authors.forename: Malou
authors.initials: M
authors.lastname: Hultcrantz
authors.forename: Konstantina
authors.initials: K
authors.lastname: Charitidi
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Barbara
authors.initials: B
authors.lastname: Canlon
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D003051:Cochlea / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000819:agonists / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009570:Nitriles / Q000627:therapeutic use; D011422:Propionates
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009570:Nitriles; C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D011422:Propionates