F. Kiesewetter et al., SEX-HORMONES AND ANTIANDROGENS INFLUENCE IN-VITRO GROWTH OF DERMAL PAPILLA CELLS AND OUTER ROOT SHEATH KERATINOCYTES OF HUMAN HAIR-FOLLICLES, Journal of investigative dermatology, 101(1), 1993, pp. 190000098-190000105
Anagen hair bulb papillae, interfollicular dermal fibroblasts, and int
erfollicular keratinocytes isolated from fronto-parietal scalp biopsie
s as well as outer root sheath keratinocytes from plucked anagen hairs
were separately grown in subculture for 14 d. The effect of different
concentrations (2.4 nM-17.3 muM) of testosterone, dihydrotestosterone
, and the antiandrogens cyproterone acetate of 17alpha-propylmesterolo
ne on growth behavior of the mesenchymal and epithelial cell types of
the hair follicle were comparatively studied by means of growth curves
, cell doubling times, and H-3-thymidine incorporation. For control, a
ll cell lines were subcultured in hormone-free medium. Testosterone an
d dihydrotestosterone (345 nM) significantly reduced proliferation of
papilla cells compared with dermal fibroblasts (p < 0.01) and outer ro
ot sheath keratinocytes compared with interfollicular keratinocytes (p
< 0.01), as well as compared with cells cultured in control medium. L
ow concentrations of 17beta-estradiol were ineffective, whereas doses
of 180 nM 17beta-estradiol increased the growth velocities of all cell
types, especially of papilla cells, compared with dermal fibroblasts.
Low doses of either cyproterone acetate (24 nM) or 17alpha-propylmest
erolone (29 nM) induced a growth enhancement, especially of papilla ce
lls and outer root sheath keratinocytes, whereas high doses of cyprote
rone (1.20 muM) and 17alpha-propylmesterolone (1.45 muM) had opposite
effects. These changes were significant between papilla cells and derm
al fibroblasts as well as between outer root sheath keratinocytes and
interfollicular keratinocytes. Applying increasing doses of androgens
to cyproterone acetate (24 nM)- or 17alpha-propylmesterolone (29 nM)-c
ontaining media neutralized the growth-stimulating effect of antiandro
gens, particularly in papilla cells and outer root sheath keratinocyte
s. However, minor differences between testosterone and dihydrotestoste
rone effects on cell growth were found. The data clearly demonstrate t
hat the changes of in vitro growth of hair follicle cells depend on th
e concentrations of androgens and antiandrogens, as higher doses of bo
th antiandrogens tested retarded the cell proliferation similar to tes
tosterone or dihydrotestosterone. The papilla cells and outer root she
ath keratinocytes reacted more sensitively to the hormones tested, the
reby confirming the concept of a distinct androgen sensitivity of thes
e specialized hair follicle cells.