Induction of vitamin D receptor mRNA expression in psoriatic plaques correlates with clinical response to 1,25-dihydroxyvitamin D3.

Psoriasis is a skin disorder characterized by hyperproliferation of epidermal keratinocytes. 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) and its analogs have been shown to inhibit keratinocyte proliferation in vitro and to be therapeutically effective for the treatment of psoriasis. Some patients with psoriasis, however, do not have a favorable response to 1 alpha,25 (OH)2D3 therapy. To evaluate the differential responsiveness to 1 alpha (OH)2D3 treatment, we examined the expression of vitamin D receptor mRNA in psoriatic lesions by reverse transcription-polymerase chain reaction using glyceraldehyde-3-phosphate dehydrogenase as an internal control. In this double-blind clinical trial, we recruited 18 patients who received topical treatment of 1 alpha,25(OH)2D3 (15 microgram/g Vaseline) or placebo on separated psoriatic lesions for 8 weeks. In patients who showed >90% clinical improvements of their psoriatic lesions with 1 alpha,25(OH)2D3 (n=9), an increase of 130+/-37% in vitamin D receptor mRNA level was observed in 1 alpha,25(OH)2D3-treated lesions when compared with the corresponding placebo controls. There was no increase in vitamin D receptor mRNA level in the lesions treated with this drug in patients who did not respond to the treatment. These data suggest that the antiproliferative activity of 1 alpha,25(OH)2D3 is closely associated with the expression of its cognate receptor.

Clinical uses for calciotropic hormones 1,25-dihydroxyvitamin D3 and parathyroid hormone-related peptide in dermatology: a new perspective.

The skin is not only the organ for the photosynthesis of vitamin D3, but also a target tissue for its activated form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Vitamin D3 is absolutely essential for the development and maintenance of a healthy skeleton. Without an adequate source of vitamin D, children develop rickets and the elderly develop osteomalacia and exacerbation of osteoporosis. 1,25(OH)2D3 is a potent inhibitor of proliferation of epidermal cells and, with its analogs, it has been developed for the successful treatment of psoriasis. Not all psoriasis patients, however, respond to 1,25(OH)2D3 and its analogs. Evidence suggests that there may be a defect in the regulation of levels of mRNA for the vitamin D receptor in patients who have partial or no response to 1,25(OH)2D3 therapy. The degree of responsiveness to 1,25(OH)2D3 therapy may also be related to the allelic variations in the vitamin D receptor gene. Parathyroid hormone-related peptide is synthesized by the epidermis and is an endogenous antiproliferative factor. Parathyroid hormone-related peptide agonists and 1,25(OH)2D3 inhibit in vitro and in vivo epidermal proliferation, whereas parathyroid hormone-related peptide antagonists stimulate both epidermal proliferation and hair growth in vivo. Therefore, the calciotropic hormones 1,25(OH)2D3 and parathyroid hormone-related peptide have wide-ranging clinical applications in dermatology.