Biphasic effect of 1,25-dihydroxyvitamin D3 on human hair follicle growth and hair fiber production in whole-organ cultures.
We have used a whole-organ culture system to investigate the effects of 1,25(OH)2D3 on human hair follicle growth and hair fiber production. Relatively low concentrations (1-10 nM) of 1,25(OH)2D3 stimulated the cumulative growth of hair follicles and hair fibers, by 52% and 36%, respectively (concentration producing 50% of the maximal response [EC50] values of 0.3 nM). The initial rates of follicle and fiber growth were increased, whereas the respective growth periods were unaffected. At higher concentrations of 1,25(OH)2D3, there was a dose-dependent inhibition of both follicle and fiber growth (IC50 values of 100 nM), in part due to reduction in the growth periods. There was a marked delay between the onset of 1,25(OH)2D-induced hair follicle and hair fiber growth inhibition. Incubation of hair follicles with 100 nM 1,25(OH)2D3 resulted in a rapid, transient inhibition of DNA synthesis (55% inhibition at 24 h), followed by a gradual return to control levels at day 4. Prolonged (> 5 h), incubation in the presence of 100 nM of 1,25 (OH)2D3 was required for follicle growth inhibition to be manifest. Ro 31-7549, a selective inhibitor of protein kinase C, did not prevent 1,25(OH)2D3-induced inhibition of hair follicle growth. These data suggest that 1,25(OH)2D3 may play a physiologic role in maintaining optimal hair follicle activity, and that elevation of 1,25(OH)2D3 may inhibit hair growth in vivo.
Harmon
C S
CS
Preclinical Dermatology Research, Hoffmann-La Roche, Nutley, New Jersey 07110.
Nevins
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TD
D002117:Calcitriol / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006197:Hair / Q000187:drug effects* / Q000254:growth & development*; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009924:Organ Culture Techniques; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013997:Time Factors
D007211:Indoles; D008301:Maleimides; D004247:DNA; D011493:Protein Kinase C; D002117:Calcitriol; C064755:Ro 31-7549