title: Renal LRP2 expression in man and chicken is estrogen-responsive.
abstract: In mammals, low-density lipoprotein receptor-related protein-2 (LRP2) is an endocytic receptor that binds multiple ligands and is essential for a wide range of physiological processes. To gain new insights into the biology of this complex protein, we have initiated the molecular characterization of the LRP2 homolog from an oviparous species, the chicken (Gallus gallus). The galline LRP2 cDNA encodes a membrane protein of 4658 residues. Overall, the galline and human proteins are 73% identical, indicating that the avian gene has been well conserved over 300 million years. Unexpectedly, LRP2 transcript and protein levels in the kidney of females and estrogen-treated roosters were significantly higher than those in untreated males. The estrogen-responsiveness of avian LRP2 may be related to the dramatic differences in lipoprotein metabolism between mature roosters and laying hens. Newly identified potential estrogen-responsive elements (ERE) in the human and galline LRP2 gene, and additional Sp1 sites present in the promoter of the chicken gene, are compatible with both direct estrogen induction via the classical ligand-induced ERE pathway and the indirect transcription factor crosstalk pathway engaging the Sp1 sites. In agreement with this assumption, estrogen induction of LRP2 was observed not only in primary cultured chicken kidney cells, but also human kidney cell lines. These findings point to novel regulatory features of the LRP2 gene resulting in sex-specific receptor expression.
authors.affiliation: Max F. Perutz Laboratories, Department of Medical Biochemistry, Medical University of Vienna, Dr. Bohr-Gasse 9/2, A-1030 Vienna, Austria.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Plieschnig
authors.forename: Eva T
authors.initials: ET
authors.lastname: Gensberger
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Bajari
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Schneider
authors.forename: Marcela
authors.initials: M
authors.lastname: Hermann
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015153:Blotting, Western; D002478:Cells, Cultured; D002645:Chickens; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D016329:Sp1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D004967:Estrogens; D007074:Immunoglobulin G; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D008156:Luciferases