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Extrarenal Sites of Calcitriol Synthesis:The Particular Role of the Skin

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Vitamin D Analogs in Cancer Prevention and Therapy

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 164))

Abstract

Calcitriol (1α,25(OH)2D3), the hormonally active form of vitamin D3(D3) is produced by a cascade of reactions, including photochemical D3synthesis in the skin and subsequent hydroxylation at the C-25 atom in the liver and finally at C-1α position in the kidney. However, there is substantial evidence for additional extrarenal sites of calcitriol synthesis. In vitro, many nonrenal cells,including bone, placenta, prostata, keratinocytes, macrophages, T-lymphocytes and several cancer cells (e.g., from lung, prostata and skin) can enzymatically convert calcidiol (25OHD3) to 1a,25(OH)2D3. We have demonstrated that keratinocytes of the skin have unique properties in the D3pathway; they are not only capable of producing D3from 7-dehydrocholesterol (7-DHC), but also generate 1α,25(OH)2D3from the substrates 25OHD3, 1a-hydroxyvitamin D3(1α-OHD3) and even D3. It is evident that keratinocytes possess at least 1α- OH-, 25OH- and 24OHase activity, which is necessary for enzymatic conversion of D3to 1α,25(OH)2D3, and the 24OHase activity for initiation of catabolism of 1α,25(OH)2D3to more polar metabolites. Thus, the skin is apparently the only extrarenal tissue where the complete UVB-induced pathway from 7-DHC to 1α,25(OH)2D3takes place under physiological circumstances.

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Authors and Affiliations

  1. Department of Dermatology, Carl Gustav Carus Medical School, Dresden University of Technology, Fetscherstr. 74, 01307, Dresden, Germany

    Bodo Lehmann

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  1. Bodo Lehmann
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  2. Michael Meurer
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Editors and Affiliations

  1. Hautklinik und Poliklinik der Universitätskliniken des Saarlandes, Kirrberger Str., 66421, Homburg/Saar

    Jörg Reichrath  & Wolfgang Tilgen  & 

  2. Frauenklinik des Universitätsklinikums der Eberhard-Karls-Universität, Calwerstr. 7, 71076, Tübingen

    Michael Friedrich

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© 2003 Springer-Verlag Berlin Heidelberg

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Lehmann, B., Meurer, M. (2003). Extrarenal Sites of Calcitriol Synthesis:The Particular Role of the Skin. In: Reichrath, J., Tilgen, W., Friedrich, M. (eds) Vitamin D Analogs in Cancer Prevention and Therapy. Recent Results in Cancer Research, vol 164. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55580-0_9

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  • DOI: https://doi.org/10.1007/978-3-642-55580-0_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-62435-3

  • Online ISBN: 978-3-642-55580-0

  • eBook Packages: Springer Book Archive

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