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      Estrogen Replacement Reduces Hearing Threshold Shifts and Cochlear Hair Cell Loss After Acoustic Overexposure in Ovariectomized Rats

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          Abstract

          Objectives.

          The relationship of estrogen (the primary female sex hormone) with hearing function has been studied in both humans and animals. However, whether estrogen levels affect hearing remains uncertain. Therefore, in this study, we investigated changes in the vulnerability of hearing to acoustic overexposure in ovariectomized female rats.

          Methods.

          Eighteen 8-week-old female Sprague-Dawley rats were separated into four groups as follows: sham ovariectomy (OP), OP only, and OP treated with low (10 µg/kg) or high doses (100 µg/kg) of estrogen. Rats in the estrogen replacement groups were given two intraperitoneal injections. Hearing thresholds were measured before noise exposure, and at 1 day and 2 weeks after exposure.

          Results.

          The hearing thresholds of the sham OP and OP-only groups were not significantly different. However, both estrogen groups showed a lower threshold shift than the OP-only group. Histological immunostaining analyses showed that hair cell loss in the 32 kHz region was more severe in the sham OP group than in the OP-only group. Furthermore, there was little or no hair cell loss in either estrogen replacement group and significantly more hair cell loss in the OP-only group.

          Conclusion.

          These results suggest that estrogen replacement may reduce the vulnerability of hearing to noise exposure in menopausal women.

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          Most cited references21

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          Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss.

          Overexposure to intense sound can cause temporary or permanent hearing loss. Postexposure recovery of threshold sensitivity has been assumed to indicate reversal of damage to delicate mechano-sensory and neural structures of the inner ear and no persistent or delayed consequences for auditory function. Here, we show, using cochlear functional assays and confocal imaging of the inner ear in mouse, that acoustic overexposures causing moderate, but completely reversible, threshold elevation leave cochlear sensory cells intact, but cause acute loss of afferent nerve terminals and delayed degeneration of the cochlear nerve. Results suggest that noise-induced damage to the ear has progressive consequences that are considerably more widespread than are revealed by conventional threshold testing. This primary neurodegeneration should add to difficulties hearing in noisy environments, and could contribute to tinnitus, hyperacusis, and other perceptual anomalies commonly associated with inner ear damage.
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            The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy

            Epidemiologic studies have previously suggested that premenopausal females have reduced incidence of cardiovascular disease (CVD) when compared to age-matched males, and the incidence and severity of CVD increases postmenopause. The lower incidence of cardiovascular disease in women during reproductive age is attributed at least in part to estrogen (E2). E2 binds to the traditional E2 receptors (ERs), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ), as well as the more recently identified G-protein-coupled ER (GPR30), and can exert both genomic and non-genomic actions. This review summarizes the protective role of E2 and its receptors in the cardiovascular system and discusses its underlying mechanisms with an emphasis on oxidative stress, fibrosis, angiogenesis, and vascular function. This review also presents the sexual dimorphic role of ERs in modulating E2 action in cardiovascular disease. The controversies surrounding the clinical use of exogenous E2 as a therapeutic agent for cardiovascular disease in women due to the possible risks of thrombotic events, cancers, and arrhythmia are also discussed. Endogenous local E2 biosynthesis from the conversion of testosterone to E2 via aromatase enzyme offers a novel therapeutic paradigm. Targeting specific ERs in the cardiovascular system may result in novel and possibly safer therapeutic options for cardiovascular protection.
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              Differential vulnerability of basal and apical hair cells is based on intrinsic susceptibility to free radicals.

              The base of the cochlea is more vulnerable to trauma than the apex as seen in the pattern of hair cell damage by cisplatin or aminoglycosides. The differential vulnerability is maintained in organotypic cultures exposed directly to these drugs, suggesting there may be an intrinsic difference in sensitivity to damage along the cochlear spiral. We therefore investigated the survival capacity of isolated outer hair cells and strips dissected from different turns of the guinea pig organ of Corti in short-term culture. Cells were stained with fluorescent indicators of viable or dead cells, calcein-AM and ethidium homodimer. After 5 h at room temperature, up to 90% of outer hair cells from the apex survived, but less than 30% from the base. In contrast, basal inner hair cells remained viable, and supporting cells survived for at least 20 h. The difference in survival capacity between basal and apical outer hair cells coincided with a significantly lower level of the antioxidant glutathione in basal outer hair cells compared with apical outer hair cells. This suggested that basal outer hair cells may be more vulnerable to free-radical damage than apical outer hair cells. The survival of basal outer hair cells was significantly improved by addition of the radical scavengers n-acetyl cysteine, p-phenylenediamine, glutathione, mannitol or salicylate. The protection by antioxidants implies that the accelerated death of basal outer hair cells is due to free-radical damage. The results support an intrinsic susceptibility to free radicals that differs among cochlear cell populations. This differential provides a rational explanation for base-to-apex gradients observed in various forms of cochlear pathology.
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                Author and article information

                Journal
                Clin Exp Otorhinolaryngol
                Clin Exp Otorhinolaryngol
                CEO
                Clinical and Experimental Otorhinolaryngology
                Korean Society of Otorhinolaryngology-Head and Neck Surgery
                1976-8710
                2005-0720
                February 2021
                15 May 2020
                : 14
                : 1
                : 61-68
                Affiliations
                [1 ]Department of Otolaryngology-Head and Neck Surgery, Dankook University Hospital, Cheonan, Korea
                [2 ]Department of Otolaryngology-Head and Neck Surgery, Dankook University College of Medicine, Cheonan, Korea
                [3 ]Beckman Laser Institute Korea, Dankook University College of Medicine, Cheonan, Korea
                Author notes
                Corresponding author: Jae Yun Jung Department of Otolaryngology-Head and Neck Surgery, Dankook University College of Medicine, 119 Dandae-ro, Dongnam-gu, Cheonan 31116, Korea Tel: +82-41-550-3973, Fax: +82-41-556-1090 E-mail: jjkingy2k@ 123456gmail.com
                [*]

                *The first two authors contributed equally to this study.

                Author information
                http://orcid.org/0000-0003-3244-9024
                http://orcid.org/0000-0003-2317-9958
                http://orcid.org/0000-0001-6984-3979
                http://orcid.org/0000-0002-6860-8042
                http://orcid.org/0000-0003-4591-2276
                http://orcid.org/0000-0002-1870-0748
                Article
                ceo-2019-01662
                10.21053/ceo.2019.01662
                7904427
                32407615
                c8afba13-2712-4c38-899c-e869e9e3fc42
                Copyright © 2021 by Korean Society of Otorhinolaryngology-Head and Neck Surgery

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 October 2019
                : 31 December 2019
                : 5 February 2020
                Categories
                Original Article

                Otolaryngology
                hearing loss,estrogen replacement therapy,ovariectomy
                Otolaryngology
                hearing loss, estrogen replacement therapy, ovariectomy

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