J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M300014-JLR200 on June 1, 2003

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Journal of Lipid Research, Vol. 44, 1633-1642, September 2003
Copyright © 2003 by American Society for Biochemistry and Molecular Biology

Molecular characterization of the first avian LDL receptor

: role in sterol metabolism of ovarian follicular cells

Susanna Hummel1, Edward G. Lynn1, Andreas Osanger2, Satoshi Hirayama3, Johannes Nimpf and Wolfgang J. Schneider4

Institute of Medical Biochemistry, Department of Molecular Genetics, University and BioCenter Vienna, Austria

4 To whom correspondence should be addressed. e-mail: wjs{at}mol.univie.ac.at

Low levels of expression and sluggish sterol-mediated regulation have been likely reasons for the failure to molecularly characterize a bona fide LDL receptor (LDLR) in egg-laying species to date. The overall structure of the chicken LDLR, delineated here by cDNA cloning, has been conserved in evolution, since hallmark properties of mammalian LDLRs are already present in the avian protein. The chicken receptor appears to prefer LDL over VLDL as ligand, in compliance with its main role in providing lipoprotein-derived cholesterol for steroid production in ovarian follicular cells. This is also compatible with the fact that estrogen administration increased hepatic LDLR expression in roosters despite dramatically stimulated VLDL production. In cultured chicken embryo fibroblasts, expression of the receptor was induced by incubation with cholesterol synthesis inhibitors such as a statin. Furthermore, preincubation of induced cells with a specific anti-receptor antibody blocks LDL endocytosis, demonstrating that the receptor is ligand-endocytosis competent. Finally, the distribution of LDLRs among the extraoocytic cell populations lends support to a three-cell model for estrogen production within the ovarian follicle.

In summary, the molecular characterization of the first avian LDLR reveals novel information about evolutionary, structural, and functional aspects of members of the supergene family of LDLR-related proteins.

Supplementary key words lipoprotein • ovary • pitavastatin


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Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.