THE METABOLISM OF TESTOSTERONE BY DERMAL PAPILLA CELLS CULTURED FROM HUMAN PUBIC AND AXILLARY HAIR-FOLLICLES CONCURS WITH HAIR-GROWTH IN 5-ALPHA-REDUCTASE DEFICIENCY

Androgens regulate the growth of many human hair follicles, but only p ubic, axillary, and scalp hair growth occur in men with 5 alpha-reduct ase deficiency. This suggests that 5 alpha-dihydrotestosterone is the active intracellular androgen in androgen-dependent follicles, except in the axilla and pubis. Since the dermal papilla plays a major regula tory role in hair follicles and may be the site of androgen action, we have investigated androgen metabolism in six primary lines of culture d dermal papilla cells from pubic and axillary hair follicles; previou s studies have shown that beard cells take up and metabolize testoster one, retaining and secreting 5 alpha-dihydrotestosterone. After 24 h p reincubation in serum-free Eagle's medium 199, 100-mm dishes of conflu ent cells were incubated for 2 h with 5 nM [1,2,6,7-H-3]testosterone. Media were collected and the cells washed with phosphate-buffered sali ne and extracted with chloroform: methanol (2:1). After the addition o f unlabeled and C-14-labeled marker steroids, the extracts were analyz ed by a two-step thin-layer chromatography system; steroid identity wa s confirmed by recrystallization to a constant H-3/C-14 ratio. Beard a nd pubic dermal papilla cells were also incubated for 24 h, and the me dium was analyzed at various times. The results from pubic and axillar y primary cell lines were similar. In both cells and media the major s teroid identified was testosterone, but significant amounts of androst enedione were present, indicating 17 beta-hydroxysteroid dehydrogenase activity; androstanedione was also identified within the cells, but a small amount of 5 alpha-dihydrotestosterone was only identified in on e pubic cell line. Beard dermal papilla cells secreted large amounts o f 5 alpha-dihydrotestosterone into the medium over 24 h in contrast to pubic cells, which produced only very small amounts. The pubic and ax illary cell results contrast with the observations of pronounced 5 alp ha-dihydrotestosterone in beard cells and confirm that androgen metabo lism in cultured dermal papilla cells reflects the parent follicle's a bility to respond to androgen in the absence of 5 alpha-reductase type II in vivo. This supports our hypothesis that androgen acts on hair f ollicles via the dermal papilla and suggests that cultured dermal papi lla cells may offer an important model system for studies of androgen action.