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Vitamin D₃ Analogs Stimulate Hair Growth in Nude Mice

Cedars-Sinai Medical Center/University of California Los Angeles School of Medicine (V.V., J.O., J.S., N.L., T.S., T.I., H.P.K.), Los Angeles, California 90048; Hoffman-LaRoche Inc. (M.U.), Nutley, New Jersey 07110; Leo Pharmaceuticals (L.B.), DK-2750 Ballerup, Denmark

Address all correspondence and requests for reprints to: James O’Kelly, Ph.D., Division of Hematology/Oncology, Cedars Sinai Medical Center, University of California Los Angeles School of Medicine, 8700 Beverly Boulevard, Los Angeles, California 90048. E-mail: okellyj{at}cshs.org.

The active form of vitamin D₃ can regulate epidermal keratinization by inducing terminal differentiation; and mice lacking the vitamin D receptor display defects leading to postnatal alopecia. These observations implicate the vitamin D₃ pathway in regulation of hair growth. We tested the ability of 1,25 dihydroxyvitamin D₃ and its synthetic analogs to stimulate hair growth in biege/nude/xid (BNX) nu/nu (nude) mice exhibiting congenital alopecia. Nude mice were treated with different vitamin D₃ analogs at doses that we had previously found to be the highest dose without inducing toxicity (hypercalcemia). The mice were monitored for hair growth and were scored according to a defined scale. Skin samples were taken for histological observation of hair follicles and for extraction of RNA and protein. Vitamin D₃ analogs dramatically stimulated the hair growth of nude mice, although parental 1,25 dihydroxyvitamin D₃ had no effect. Hair growth occurred in a cyclical pattern, accompanied by formation of normal hair follicles and increased expression of certain keratins (Ha7, Ha8, and Hb3). Vitamin D₃ analogs seem to act on keratinocytes to initiate hair follicle cycling and stimulate hair growth in mice that otherwise do not grow hair.

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