1 alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is known to be a hormonally active form of vitamin D3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 alpha,24(R)-dihydroxyvitamin D3 (1,24(OH)2D3), a novel synthetic derivative of vitamin D3, is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH)2D3 had the same affinity as 1,25(OH)2D3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH)2D3 induced their differentiation in a time- and dose-dependent manner, as determined by the formation of a cornified envelope and an increase in the activity of transglutaminase. 1,24(OH)2D3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH)2D3 were similar to, or rather more than, those of physiologically active 1,25(OH)2D3. However, 1,24(OH)2D3 was found to cause less hypercalcemia than 1,25(OH)2D3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.

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