Skin as the Site of Vitamin D Synthesis and Target Tissue for 1,25-Dihydroxyvitamin D3

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Abstract
• Vitamin D is a hormone, not a vitamin. The skin is responsible for producing vitamin D. During exposure to sunlight, ultraviolet radiation penetrates into the epidermis and photolyzes provitamin D3to previtamin D3. Previtamin D3can either isomerize to vitamin D3or be photolyzed to lymisterol and tachysterol. Vitamin D is also sensitive to sunlight and is photolyzed to 5,6-transvitamin D3, suprasterol I, and suprasterol II. In Boston, solar irradiation only produces previtamin D3in the skin between the months of March and October. Aging, sunscreens, and melanin all diminish the capacity of the skin to produce previtamin D3. Once formed, vitamin D3enters the circulation and is sequentially metabolized to 25-hydroxyvitamin D3and 1,25-dihydroxyvitamin D3(1,25-[OH]2-D3). The epidermis possesses receptors for 1,25-(OH)2-D3.1,25-(OH)2-D3D3inhibits the proliferation of cultured keratinocytes and induces them to terminally differentiate. The topical or oral administration of 1,25-(OH)2-D3has proved to be effective for the treatment of psoriasis. Therefore, the skin is the site for the synthesis of vitamin D and a target tissue for its active metabolite. The successful use of 1,25-(OH)2-D3for the treatment of psoriasis heralds a new approach for the treatment of this enigmatic disorder. (Arch Dermatol1987;123:1677-1683a)