Oestrogen receptors (ERs) are present in human osteoblasts and mediate anti-resorptive effects on bone. Human osteoblast-like cells derived from different aged healthy female donors not on hormone replacement therapy were utilized under well-defined conditions in vitro to investigate ER function and levels. Treatment with 0.1 nM oestradiol-17β of cell strains derived from eight young women (less than 50 years of age) increased hydroxyproline levels significantly [an average (2.2±0.1 S.E.M.)-fold increase], whereas cells derived from nine older women (more than 50 years of age) were not significantly affected. Similarly, cell strains, derived from younger women, transfected with a consensus oestrogen-responsive element linked to chloramphenicol acetyltransferase exhibited a greater response to oestrogen than strains derived from older women. When basal ERα levels were measured by enzyme immunoassay and normalized on a per cell basis, osteoblast-like strains derived from younger women (n = 24) had a mean value of 2.54±0.16 fmol of ERα per 106 cells. In contrast, strains derived from older women (n = 20) had a mean value of 5.44±0.48 fmol of ERα per 106 cells. An age-related increase in ERα number was also observed in human skin-derived fibroblasts and directly in dermal biopsies from women not on hormone replacement therapy. The results demonstrate ligand concentration-dependent ERα induction and indicate a loss of receptor regulation and diminution of ligand–receptor signal transduction with increasing donor age.
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August 1998
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Research Article|
August 01 1998
Age-related changes in human oestrogen receptor α function and levels in osteoblasts
Michael A. ANKROM;
Michael A. ANKROM
1
*Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, U.S.A.
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Julie A. PATTERSON;
*Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, U.S.A.
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Patricia Y. d'AVIS;
Patricia Y. d'AVIS
*Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, U.S.A.
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Ulrich K. VETTER;
Ulrich K. VETTER
†Allgemeines Krankenhaus Heidberg, Tangstedter Landstrasse 400, 22413 Hamburg, Federal Republic of Germany
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Marc R. BLACKMAN;
Marc R. BLACKMAN
‡Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21224, U.S.A.
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Paul D. SPONSELLER;
Paul D. SPONSELLER
§Department of Orthopaedics, Johns Hopkins University School of Medicine, Baltimore, MD 21224, U.S.A.
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Matthew TAYBACK;
Matthew TAYBACK
*Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, U.S.A.
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Pamela Gehron ROBEY;
Pamela Gehron ROBEY
‖Craniofacial and Skeletal Diseases Branch, National Institute of Dental Research, N.I.H. Bethesda, MD 20892, U.S.A.
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Jay R. SHAPIRO;
Jay R. SHAPIRO
*Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, U.S.A.
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Neal S. FEDARKO
Neal S. FEDARKO
3
*Division of Geriatrics and Gerontology, Department of Medicine, Johns Hopkins University School of Medicine, 5501 Hopkins Bayview Circle, Baltimore, MD 21224, U.S.A.
3To whom correspondence should be addressed (e-mail ndarko@welchlink.welch.jhu.edu).
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Publisher: Portland Press Ltd
Received:
February 06 1998
Revision Received:
April 20 1998
Accepted:
May 06 1998
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 1998
1998
Biochem J (1998) 333 (3): 787–794.
Article history
Received:
February 06 1998
Revision Received:
April 20 1998
Accepted:
May 06 1998
Citation
Michael A. ANKROM, Julie A. PATTERSON, Patricia Y. d'AVIS, Ulrich K. VETTER, Marc R. BLACKMAN, Paul D. SPONSELLER, Matthew TAYBACK, Pamela Gehron ROBEY, Jay R. SHAPIRO, Neal S. FEDARKO; Age-related changes in human oestrogen receptor α function and levels in osteoblasts. Biochem J 1 August 1998; 333 (3): 787–794. doi: https://doi.org/10.1042/bj3330787
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