1,24(R)‐Dihydroxyvitamin D 3 , a Novel Active Form of Vitamin D 3 with High Activity for Inducing Epidermal Differentiation but Decreased Hypercalcemic Activity

1 α ,25‐Dihydroxyvitamin D 3 (1,25(OH) 2 D 3 ) is known to be a hormonally active form of vitamin D 3 in the regulation of intracellular and extracellular calcium levels and of differentiation of myeloid cells and epidermal keratinocytes. We found that 1 α ,24(R)‐dihydroxyvitamin D 3 (1,24(OH) 2 D 3 ), a novel synthetic derivative of vitamin D 3 , is also active in regulating the differentiation of epidermal keratinocytes. 1,24(OH) 2 D 3 had the same affinity as 1,25(OH) 2 D 3 for a receptor isolated from the epidermis of newborn mice. The incubation of mouse epidermal keratinocytes with 1,24(OH) 2 D 3 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) 2 D 3 inhibited DNA synthesis of epidermal keratinocytes and also increased their cytosolic calcium level. These effects of 1,24(OH) 2 D 3 were similar to, or rather more than, those of physiologically active 1,25(OH) 2 D 3 . However, 1,24(OH) 2 D 3 was found to cause less hypercalcemia than 1,25(OH) 2 D 3 when administrated intravenously to rats, suggesting its possible therapeutic value in psoriasis.