PTERINS IN HUMAN HAIR FOLLICLE CELLS AND IN THE SYNCHRONIZED MURINE HAIR CYCLE

Human dermal papilla cells (HDPC) express mRNA for the key enzymes for de novo synthesis/recycling and regulation of the pterin (6R)-L-eryth ro-5,6,7,8-tetrahydrobiopterin (6BH(4)), HDPC had significantly higher enzyme activities and 6BH(4) levels in a comparative study with derma l fibroblasts, epidermal melanocytes, and keratinocytes under in vitro conditions. In addition, a significantly more rapid uptake of C-14-L- phenylalanine was demonstrated in HDPC compared with fibroblasts, wher eas the differences in turnover to L-tyrosine were insignificant, sugg esting a pooling of L-phenylalanine in HDPC, These results suggested t hat HDPC driven 6BH(4) synthesis could be of major functional importan ce in the hair cycle. In order to follow this hypothesis in vivo, expr ession of enzyme activities and levels of the produced cofactor during the synchronized hair cycle were determined employing the murine mode l C57BL/6, These data revealed a significantly increased de novo synth esis for 6BH(4) via GTP-cyclohydrolase I concomitant with high levels of 6BH(4), and the induction of phenylalanine hydroxylase activities d uring the telogen/early anagen stage (days 0-1), Pterin levels and enz yme activities fall on day 3 and plateau during the rest of the entire cycle, In addition, thioredoxin reductase and glutathione reductase a ctivities were measured, where the latter enzyme remained constant but thioredoxin reductase activities showed a biphasic behavior. The firs t peak coincided with the induction of 6BH(4) de novo synthesis at the beginning of the hair cycle. The second peak was observed at mid-anag en, when melanogenesis takes place. Taken together, our results show t he presence of autocrine pterin synthesis/recycling in human hair foll icle cells under in vitro conditions, and a possible role for 6BH(4) i n the synchronized murine hair cycle.