22-OXA CALCITRIOL IS A LESS POTENT REGULATOR OF KERATINOCYTE PROLIFERATION AND DIFFERENTIATION DUE TO DECREASED CELLULAR UPTAKE AND ENHANCED CATABOLISM

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 vit ro. 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 disea ses, such as psoriasis, that respond to the antiproliferative, prodiff erentiating actions of 1,25(OH)(2)D-3. To determine the potential usef ulness of OCT in hyperproliferative skin diseases, we compared the abi lity of OCT to that of 1,25(OH)(2)D-3 with respect to regulation of ke ratinocyte proliferation and differentiation in vitro. These studies w ere performed in serum-free media to eliminate differences in potency secondary to differences in binding to the serum vitamin D-binding pro tein, We observed that OCT was considerably less effective than 1,25(O H)(2)D-3 in inhibiting keratinocyte proliferation and stimulating diff erentiation, The decreased potency of OCT appeared to be due to decrea sed uptake and increased catabolism rather than decreased afinity for the vitamin D receptor. We conclude that under the conditions of our e xperiments OCT was less potent than 1,25(OH)(2)D-3 because it failed t o achieve comparable concentrations within the cell.