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17β-Estradiol increases the receptor number and modulates the action of 1,25-dihydroxyvitamin D3 in human osteosarcoma-derived osteoblast-like cells

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Abstract

It is well known that 17β-estradiol (E2) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) have important roles in bone metabolism. This study was undertaken to examine E2 regulation of 1,25(OH)2D3 receptor (VDR) expression and the biological action of 1,25(OH)2D3 in human osteoblast-like cells. When human osteosarcoma-derived osteoblast-like cells were treated with varying concentrations of E2, the VDR levels increased by up to 100% in a dose-dependent manner. VDR levels significantly increased at 10 nM E2 and this increase plateaued at 100 nM E2. E2-dependent increase of VDR was time dependent, plateauing, at 24 hours and was maintained for at least 48 hours in human osteoblast-like cells. Scatchard analysis showed that E2 increased the number of VDR (12.3±0.4 versus 26.5±0.3 fmol/mg protein; mean ±SE of three independent experiments) rather than the Kd (0.15±0.02 versus 0.16±0.01 nM; mean±SE of three independent experiments). Tamoxifen (50 nM), a specific competitor with E2, completely abolished the E2-induced increase of VDR. The levels of VDR mRNA (4.5 kb) from the cells increased in a dose-dependent manner after E2 treatment. With regard to the biological effects, E2 increased by 10–25% the inhibitory effect of 1,25(OH)2D3 on cell growth. However, E2 did not increase the stimulation of alkaline phosphatase activity by 1,25(OH)2D3. The present study suggests that E2 modulates the biological action of 1,25(OH)2D3 through VDR levels in bone cells.

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Authors and Affiliations

  1. Department of Orthopaedics, NTT Sapporo Hospital, South 1 West 15, 060, Sapporo, Japan

    M. Ishibe

  2. Department of Pathology, Hokkaido University School of Medicine, 060, Sapporo, Japan

    T. Nojima

  3. Department of Biochemistry, Hokkaido University School of Medicine, 060, Sapporo, Japan

    T. Ishibashi

  4. Institute of Immunological Science, Hokkaido University, 060, Sapporo, Japan

    T. Koda

  5. Department of Orthopaedics, Hokkaido University School of Medicine, 060, Sapporo, Japan

    K. Kaneda

  6. Department of Orthopaedics, University of Rochester, 14620, Rochester, New York, USA

    R. N. Rosier & J. E. Puzas

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  2. T. Nojima
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  7. J. E. Puzas
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Ishibe, M., Nojima, T., Ishibashi, T. et al. 17β-Estradiol increases the receptor number and modulates the action of 1,25-dihydroxyvitamin D3 in human osteosarcoma-derived osteoblast-like cells. Calcif Tissue Int 57, 430–435 (1995). https://doi.org/10.1007/BF00301946

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  • DOI: https://doi.org/10.1007/BF00301946

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