C Holliday, RS Mason
(collaborators: G Posner, Dept of Chemistry, Johns Hopkins Univ, Baltimore, MD, USA; G Halliday, Dept of Dermatology)
Although vitamin D compounds are best known for their role in bone mineralization, the active metabolite of vitamin D,(1,25)dihydroxyvitamin D3 (1,25(OH)2D3), has been shown to enhance the differentiation of a wide variety of cell types, including epidermal skin cells. Compounds related to 1,25(OH)2D3 have recently been found to be useful in the treatment of psoriasis, a hyperproliferative disorder of skin. Newer analogs of 1,25(OH)2D3 have been synthesized by G Posner with the aim of retaining the differentiating bioactivity of this class of compounds but reducing their propensity to cause hypercalcaemia. In studies with epidermal cells in tissue culture, the 3 new analogs tested were shown to be at least as potent as 1,25(OH)2D3 in stimulating differentiation of this cell type. Exposure of these cells to UV irradiation also stimulates differentiation, that is, cornification of epidermal cells. After UV exposure, cornification was higher in epidermal cells maintained in the presence of the vitamin D analogs than those maintained in the solvent vehicle, though off a higher base. These results suggest that the compounds may have application in the treatment of some skin disorders and may possibly enhance the capacity to adapt to UV irradiation. In earlier studies in mice, it was found that pigmentation in response to UV irradiation was increased when retinoic acid was painted onto the skin. The experiments using human pigment cells also showed that under some circumstances, pigmentary activity was higher after UV exposure in the presence of retinoic acid than in the presence of vehicle alone.