Kiesewetter F, Arai A, Schell H
Department of Dermatology, University of Erlangen-Nürnberg, Germany.
J Invest Dermatol. 1993 Jul;101(1 Suppl):98S-105S. doi: 10.1111/1523-1747.ep12363015.
Anagen hair bulb papillae, interfollicular dermal fibroblasts, and interfollicular keratinocytes isolated from fronto-parietal scalp biopsies 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 microM) of testosterone, dihydrotestosterone, and the antiandrogens cyproterone acetate or 17 alpha-propylmesterolone 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 3H-thymidine incorporation. For control, all cell lines were subcultured in hormone-free medium. Testosterone and dihydrotestosterone (345 nM) significantly reduced proliferation of papilla cells compared with dermal fibroblasts (p < 0.01) and outer root sheath keratinocytes compared with interfollicular keratinocytes (p < 0.01), as well as compared with cells cultured in control medium. Low concentrations of 17 beta-estradiol were ineffective, whereas doses of 180 nM 17 beta-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 17 alpha-propylmesterolone (29 nM) induced a growth enhancement, especially of papilla cells and outer root sheath keratinocytes, whereas high doses of cyproterone (1.20 microM) and 17 alpha-propylmesterolone (1.45 microM) had opposite effects. These changes were significant between papilla cells and dermal fibroblasts as well as between outer root sheath keratinocytes and interfollicular keratinocytes. Applying increasing doses of androgens to cyproterone acetate (24 nM)- or 17 alpha-propylmesterolone (29 nM)-containing media neutralized the growth-stimulating effect of antiandrogens, particularly in papilla cells and outer root sheath keratinocytes. However, minor differences between testosterone and dihydrotestosterone effects on cell growth were found. The data clearly demonstrate that the changes of in vitro growth of hair follicle cells depend on the concentrations of androgens and antiandrogens, as higher doses of both antiandrogens tested retarded the cell proliferation similar to testosterone or dihydrotestosterone. The papilla cells and outer root sheath keratinocytes reacted more sensitively to the hormones tested, thereby confirming the concept of a distinct androgen sensitivity of these specialized hair follicle cells.
从额顶头皮活检中分离出的生长期毛囊球部乳头、毛囊间真皮成纤维细胞和毛囊间角质形成细胞，以及从拔除的生长期毛发中获取的外根鞘角质形成细胞，分别进行传代培养14天。通过生长曲线、细胞倍增时间和3H-胸腺嘧啶核苷掺入法，比较研究了不同浓度（2.4 nM - 17.3 microM）的睾酮、双氢睾酮以及抗雄激素醋酸环丙孕酮或17α-丙基去甲睾酮对毛囊间充质和上皮细胞类型生长行为的影响。作为对照，所有细胞系均在无激素培养基中传代培养。与真皮成纤维细胞相比，睾酮和双氢睾酮（345 nM）显著降低了乳头细胞的增殖（p < 0.01）；与毛囊间角质形成细胞相比，也显著降低了外根鞘角质形成细胞的增殖（p < 0.01），与在对照培养基中培养的细胞相比也是如此。低浓度的17β-雌二醇无效，而180 nM的17β-雌二醇剂量与真皮成纤维细胞相比，增加了所有细胞类型的生长速度，尤其是乳头细胞。低剂量的醋酸环丙孕酮（24 nM）或17α-丙基去甲睾酮（29 nM）可诱导生长增强，尤其是乳头细胞和外根鞘角质形成细胞，而高剂量的醋酸环丙孕酮（1.20 microM）和17α-丙基去甲睾酮（1.45 microM）则有相反的作用。这些变化在乳头细胞与真皮成纤维细胞之间以及外根鞘角质形成细胞与毛囊间角质形成细胞之间均具有显著性。向含有醋酸环丙孕酮（24 nM）或17α-丙基去甲睾酮（29 nM）的培养基中增加雄激素剂量，可中和抗雄激素的生长刺激作用，尤其是在乳头细胞和外根鞘角质形成细胞中。然而，发现睾酮和双氢睾酮对细胞生长的影响存在细微差异。数据清楚地表明，毛囊细胞体外生长的变化取决于雄激素和抗雄激素的浓度，因为所测试的两种抗雄激素的高剂量均会抑制细胞增殖，类似于睾酮或双氢睾酮。乳头细胞和外根鞘角质形成细胞对所测试的激素反应更敏感，从而证实了这些特殊毛囊细胞具有明显雄激素敏感性的概念。
