Estrogen and the inner ear: megalin knockout mice suffer progressive hearing loss

Item Type:	Article
Title:	Estrogen and the inner ear: megalin knockout mice suffer progressive hearing loss
Creators Name:	Koenig, O. and Ruettiger, L. and Mueller, M. and Zimmermann, U. and Erdmann, B. and Kalbacher, H. and Gross, M. and Knipper, M.
Abstract:	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 beta-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 beta-estrogen is taken up into the strial marginal cells; however, in megalin-deficient mice the uptake of FITC-labeled beta-estrogen is reduced. This highlights beta-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.
Keywords:	Cochlea, Stria vascularis, LDL-receptor, Sex hormone, Presbycosis, Animals, Mice, Rats
Source:	FASEB Journal
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Volume:	22
Number:	2
Page Range:	410-417
Date:	February 2008
Official Publication:	https://doi.org/10.1096/fj.07-9171com
PubMed:	View item in PubMed

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