22-oxa calcitriol (OCT) is a recently synthesized analog of calcitriol (1,25(OH)(2)D-3) with potent biologic actions both in vivo and in vitro. Because it is considerably less hypercalcemic than 1,25(OH)(2)D-3 when given in vivo, OCT is of potential use for the treatment of diseases, such as psoriasis, that respond to the antiproliferative, prodifferentiating actions of 1,25(OH)(2)D-3. To determine the potential usefulness of OCT in hyperproliferative skin diseases, we compared the ability of OCT to that of 1,25(OH)(2)D-3 with respect to regulation of keratinocyte proliferation and differentiation in vitro. These studies were performed in serum-free media to eliminate differences in potency secondary to differences in binding to the serum vitamin D-binding protein, We observed that OCT was considerably less effective than 1,25(OH)(2)D-3 in inhibiting keratinocyte proliferation and stimulating differentiation, The decreased potency of OCT appeared to be due to decreased uptake and increased catabolism rather than decreased afinity for the vitamin D receptor. We conclude that under the conditions of our experiments OCT was less potent than 1,25(OH)(2)D-3 because it failed to achieve comparable concentrations within the cell.
