Estrogen and the inner ear: megalin knockout mice suffer progressive hearing loss Ovidiu König * ,1 , Lukas Rüttiger † ,1 , Marcus Müller ‡ , Ulrike Zimmermann † , Bettina Erdmann || , Hubert Kalbacher § , Manfred Gross * and Marlies Knipper † ,2 * Audiology and Phoniatry, Charité University Clinic Berlin, Campus Benjamin Franklin, Berlin, Germany; † Molecular Neurobiology and Cell Biology of the Inner Ear and ‡ Regenerative Biology, Department of Otorhinolaryngology, Hearing Research Center Tübingen (THRC), and § Medical and Natural Sciences Research Centre, University of Tübingen, Tübingen, Germany; and || Electron Microscopy, Max-Delbrück-Center for Molecular Medicine, Berlin-Buch, Germany 2 Correspondence: Universitäts-HNO-Klinik, Elfriede-Aulhorn-Straße 5, D-72076 Tübingen, Germany. E-mail: marlies.knipper@uni-tuebingen.de Megalin, the largest member of the low-density lipoprotein receptor-related protein family, functions as an endocytic receptor for a variety of essential lipophilic metabolites, including the steroid hormone estrogen. In the cochlea, megalin is strongly expressed within the marginal cells of the stria vascularis, and previous studies demonstrated that β-estrogen receptors are also expressed in megalin-expressing marginal cells. In the present study, we demonstrate that homozygous megalin mutant mice exhibit profound hearing loss at 3 months of age associated with features of presbycusis, enrichment of lipofuscin granules, and a reduced number of microvilli in marginal cells of the stria vascularis. FITC-labeled β-estrogen is taken up into the strial marginal cells; however, in megalin-deficient mice the uptake of FITC-labeled β-estrogen is reduced. This highlights β-estrogen as a possible carrier-bound candidate ligand for megalin and supports the concept that estrogen may function via megalin within the inner ear. A crucial role of megalin in hearing should be considered and the megalin/estrogen interaction needs to be discussed in the context of early presbycusis in estrogen-deficient humans and mice.—König, O., Rüttiger, L., Müller, M., Zimmermann, U., Erdmann, B., Kalbacher, H., Gross, M., Knipper, M. Estrogen and the inner ear: megalin knockout mice suffer progressive hearing loss. Key Words: cochlea • stria vascularis • LDL-receptor • sex hormone • presbycusis
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Estrogen and the inner ear: megalin knockout mice suffer progressive hearing loss
König, Ovidiu; Rüttiger, Lukas; Müller, Marcus; Zimmermann, Ulrike; Erdmann, Bettina; Kalbacher, Hubert; Gross, Manfred; Knipper, Marlies
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, Volume 22 (2): 410
Fed of American Socs for Experimental Biology – Feb 1, 2008
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