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Effects of loss of classical estrogen response element signaling on bone in male mice.

Effects of loss of classical estrogen response element signaling on bone in male mice. Research Abstract Details 

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  • Effects of loss of classical estrogen response element signaling on bone in male mice. Abstract Text:

    farhan a syedFarhan A Syed,daniel g fraserDaniel G Fraser,thomas c spelsbergThomas C Spelsberg,clifford j rosenClifford J Rosen,andree krustAndree Krust,pierre chambonPierre Chambon,j larry jamesonJ Larry Jameson,sundeep khoslaSundeep Khosla,

    The role of estrogen signaling in the male skeleton via estrogen receptor (ER)-alpha is now well established. ERalpha can elicit responses through either classical estrogen response elements (ERE) pathways or nonclassical, non-ERE pathways. In the present study, we examined the effects of either the attenuation or loss of classical ERalpha signaling on the murine male skeleton. To accomplish this, we crossed male mice heterozygous for a knock-in mutation [nonclassical ERalpha knock-in (NERKI)], which abolishes the ERE-mediated pathway with female heterozygous ERalpha knockout mice (ERalpha+/-) and studied the F1 generation ERalpha+/+, ERalpha+/-, ERalpha+/NERKI, and ERalpha-/NERKI male progeny longitudinally using bone density and histomorphometry. The only ERalpha allele present in ERalpha-/NERKI mice is incapable of classical ERE-mediated signaling, whereas the heterozygous ERalpha+/NERKI mice have both one intact ERalpha and one NERKI allele. As compared with ERalpha+/+ littermates (n=10/genotype), male ERalpha+/NERKI and ERalpha-/NERKI mice displayed axial and appendicular skeletal osteopenia at 6, 12, 20, and 25 wk of age, as demonstrated by significant reductions in total bone mineral density (BMD) at representative sites (areal BMD by dual-energy x-ray absorptiometry at the lumbar vertebrae and femur and volumetric BMD by peripheral quantitative computed tomography at the tibia; P<0.05-0.001 vs. ERalpha+/+). The observed osteopenia in these mice was evident in both trabecular and cortical bone compartments. However, these decreases were more severe in mice lacking classical ERalpha signaling (ERalpha-/NERKI mice), compared with mice in which one wild-type ERalpha allele was present (ERalpha+/NERKI mice). Collectively, these data demonstrate that classical ERalpha signaling is crucial for the development of the murine male skeleton.

    Effects of loss of classical estrogen response element signaling on bone in male mice. Publishing Authors By Initials

    fa syedFA Syed,dg fraserDG Fraser,tc spelsbergTC Spelsberg,cj rosenCJ Rosen,a krustA Krust,p chambonP Chambon,jl jamesonJL Jameson,s khoslaS Khosla,

    For similar biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research abstracts see: biological phenomena, cell phenomena, and immunity: cell physiology: cell communication: signal transduction research

    PUBMED ID PMID:

    MEDLINE DATE:

    Effects of loss of classical estrogen response element signaling on bone in male mice. Journal Published:

    PUBLICATION TYPE: Research Support, N.I.H., Extr

    Journal: Endocrinology

    VOLUME: 148

    Page Numbers: 1902-10

    Journal Abbreviation: Endocrinology

    ISSN: 0013-7227

    DAY: 4

    MONTH: 01

    YEAR: 2007

    Effects of loss of classical estrogen response element signaling on bone in male mice. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 375040

    Effects of loss of classical estrogen response element signaling on bone in male mice. Keywords Mesh Terms:

    KEYWORDS: Signal Transduction

    MESH TERMS: physiology

    Chemical & Substance for Abstract: Effects of loss of classical estrogen response element signaling on bone in male mice. Information

    Substance Name: Estrogen Receptor alpha

    Registry Number: 0

    Grant and Affiliation Information for Effects of loss of classical estrogen response element signaling on bone in male mice.

    AFFILIATION: Endocrine Research Unit, Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, Minnesota 55905, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NICHD

    GRANT: P01 HD21921

    ACRONYM: HD

    MEDLINETA: Endocrinology

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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