It is now appreciated that 1,25(OH)2D3 may have a multitude of physiologic and pharmacologic functions. There are a variety of tissues and cells that possess nuclear receptors for 1,25(OH)2D3. Although the exact physiologic role of these nuclear receptors are unknown at the present time, it is recognized that 1,25(OH)2D3 will inhibit the proliferation and induce terminal differentiation of some cells that possess its receptor. The skin is not only the organ responsible for the synthesis of vitamin D3, but it can also act as a target tissue for 1,25(OH)2D3. When cultured human keratinocytes are incubated with 1,25(OH)2D3 this hormone inhibits in a dose- dependent manner proliferation and induces terminal differentiation. Based upon these and other observations, 1,25(OH)2D3 and its analogs have been evaluated for the treatment of the hyperproliferative skin disease psoriasis. Several clinical trials have revealed that the topical and oral administration of 1,25(OH)2D3 and its analogs are effective for treating this skin disorder. The goal of this research program is to better understand the biochemistry and pharmacology of 1,25(OH)2D3 and its analogs on psoriatic skin. This will be accomplished by : 1) evaluating the biologic activity of 1,25(OH)2D3 in cultured psoriatic fibroblasts and keratinocytes, 2) determining the metabolism of 3H-1,25(OH)2D3 and 3H-25-OH-D3 in cultured human keratinocytes, and 3) evaluating in vivo and in vitro 1,25(OH)2D3 analogs that have selective activity on antiproliferation and differentiation as possible therapeutic modalities for treating this skin disorder.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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General Medicine B Study Section (GMB)
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Boston University
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Chen, T C; Holick, M F (2000) Hexafluoro-1,25-dihydroxyvitamin D3 has markedly increased potency in inhibiting proliferation of cultured human keratinocytes compared with 1,25-dihydroxyvitamin D3. Br J Dermatol 143:72-8
Chen, T C; Persons, K S; Lu, Z et al. (2000) An evaluation of the biologic activity and vitamin D receptor binding affinity of the photoisomers of vitamin D3 and previtamin D3. J Nutr Biochem 11:267-72
Schilli, M B; Ray, S; Paus, R et al. (1997) Control of hair growth with parathyroid hormone (7-34). J Invest Dermatol 108:928-32
Holick, M F; Chen, M L; Kong, X F et al. (1996) Clinical uses for calciotropic hormones 1,25-dihydroxyvitamin D3 and parathyroid hormone-related peptide in dermatology: a new perspective. J Investig Dermatol Symp Proc 1:1-9
Chen, M L; Perez, A; Sanan, D K et al. (1996) Induction of vitamin D receptor mRNA expression in psoriatic plaques correlates with clinical response to 1,25-dihydroxyvitamin D3. J Invest Dermatol 106:637-41
Perez, A; Raab, R; Chen, T C et al. (1996) Safety and efficacy of oral calcitriol (1,25-dihydroxyvitamin D3) for the treatment of psoriasis. Br J Dermatol 134:1070-8
Perez, A; Chen, T C; Turner, A et al. (1996) Efficacy and safety of topical calcitriol (1,25-dihydroxyvitamin d3) for the treatment of psoriasis. Br J Dermatol 134:238-46
Chen, T C; Persons, K; Liu, W W et al. (1995) The antiproliferative and differentiative activities of 1,25-dihydroxyvitamin D3 are potentiated by epidermal growth factor and attenuated by insulin in cultured human keratinocytes. J Invest Dermatol 104:113-7
Tian, X Q; Chen, T C; Holick, M F (1995) 1,25-dihydroxyvitamin D3: a novel agent for enhancing wound healing. J Cell Biochem 59:53-6
Holick, M F (1995) Noncalcemic actions of 1,25-dihydroxyvitamin D3 and clinical applications. Bone 17:107S-111S

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