Vitamin D3 and its synthetic analogue secocholestra-trien-1,2, 24-triol influence the metabolism and the isomerization of retinoic acid in human keratinocytes.

Vitamin D and vitamin A acid share metabolic pathways thereby influencing their benefit as a given drug. Little is known concerning their metabolic interactions in epidermal cells. We compared the influence of 1,25-dihydroxycholecalciferol (vitamin D3 - VD3) and its synthetic analogue secocholestra-trien-1,3,24-triol (tacalcitol - TAC) in combination with different calcium concentrations (Ca) on the metabolism and the isomerization of retinoic acid (RA) in cultured primary human keratinocytes. After preincubation with 0.09, 0.6 and 1.2 mM Ca for 24 h, followed by the addition of 10(-6), 10(-8) or 10(-10) M VD3 or TAC, we added 10(-5) M 13-cis-RA (isotretinoin). 24 h later, concentrations of RA isomers and oxidated RA metabolites were measured by RP-HPLC. VD3 (10(-6) M) inhibited the isomerization of 13-cis-RA to all-trans-RA (tretinoin) and 9-cis-RA independently from the Ca concentration in the culture medium. 10(-6)-10(-10) M TAC equally inhibit the 4-hydroxylation of all-trans-RA significantly (12.8 vs. 6.7% of total RA), thereby reducing the amount of irreversible inactivated 4-oxo-all-trans-RA, leading to a higher persistence of all-trans-RA, the active hormone. Both VD3 and its analogue TAC influence the metabolism of RA, a well-known regulator of epithelial cell proliferation and differentiation processes, in two distinct ways. Further studies are necessary to test the hypothesis that the hormone activity of RA can be increased by concomitant treatment with VD3 which prolongs the persistence of 13-cis-RA, and TAC elevating the intracellular concentration of all-trans-RA.