Thornton M J, Hamada K, Messenger A G, Randall V A
Department of Biomedical Sciences, University of Bradford, UK.
J Invest Dermatol. 1998 Nov;111(5):727-32. doi: 10.1046/j.1523-1747.1998.00396.x.
Androgens stimulate many hair follicles, e.g., beard, but may cause regression on the scalp; occipital areas are considered androgen independent. The mesenchyme-derived dermal papilla that regulates the hair follicle is considered the site of androgen action. Because hair size has been clearly related to dermal papilla size, one of the key functions androgens must regulate is the size of the dermal papilla. This implies that androgens stimulate dermal papilla cells to divide or to secrete autocrine mitogenic factors. As physiologic levels of androgens do not stimulate mitogenesis in cultured dermal papilla cells, this study was designed to determine whether dermal papilla cells cultured from human hair follicles with different responses to androgens in vivo, i.e., androgen-dependent beard and androgen-independent nonbalding scalp, produce soluble autocrine mitogenic factors and, if so, whether either cell type altered their secretion in response to testosterone in vitro. Conditioned medium was prepared by incubating individual primary lines of cells for 24 h with, and without, testosterone (10(-10)-10(-5) M). All conditioned media significantly increased [3H] thymidine incorporation by other dermal papilla cells; trypsin treatment significantly reduced the effect. Although both beard and scalp cell conditioned media had a similar stimulatory potential, beard cells incorporated approximately double the [3H]thymidine of scalp cells, in both types of media. Physiologic levels of testosterone increased mitogenic factor production by beard, but not scalp cells; only beard cells responded to these factor(s). Testosterone added after conditioning had no effect, indicating stimulation was not a synergistic effect of testosterone and conditioned medium. Thus, both beard and scalp cells release similar autocrine growth factor(s), but their response to these factor(s) is determined by their in vivo origin. Testosterone in vitro stimulates secretion of an autocrine growth factor(s) by beard, but not scalp cells, to which only beard cells are able to respond, reflecting the responses to androgens in vivo. These factors may be involved in the key increase of dermal papilla size necessary for androgen-induced changes in hair size.
雄激素可刺激许多毛囊,如胡须毛囊,但可能导致头皮毛囊退化;枕部区域被认为对雄激素不敏感。调节毛囊的间充质来源的真皮乳头被认为是雄激素作用的部位。由于毛发大小与真皮乳头大小明显相关,雄激素必须调节的关键功能之一就是真皮乳头的大小。这意味着雄激素刺激真皮乳头细胞分裂或分泌自分泌促有丝分裂因子。由于生理水平的雄激素不会刺激培养的真皮乳头细胞发生有丝分裂,本研究旨在确定从对体内雄激素有不同反应的人毛囊中培养的真皮乳头细胞,即雄激素依赖的胡须毛囊和雄激素不敏感的非秃头皮毛囊,是否产生可溶性自分泌促有丝分裂因子,如果是,两种细胞类型在体外是否会因睾酮而改变其分泌。通过将单个原代细胞系在有和没有睾酮(10⁻¹⁰ - 10⁻⁵ M)的情况下孵育24小时来制备条件培养基。所有条件培养基均显著增加了其他真皮乳头细胞的[³H]胸苷掺入量;胰蛋白酶处理显著降低了这种作用。尽管胡须和头皮细胞的条件培养基具有相似的刺激潜力,但在两种类型的培养基中,胡须细胞掺入的[³H]胸苷约为头皮细胞的两倍。生理水平的睾酮增加了胡须细胞而非头皮细胞的促有丝分裂因子产生;只有胡须细胞对这些因子有反应。在制备条件培养基后添加睾酮没有效果,表明刺激不是睾酮和条件培养基的协同作用。因此,胡须和头皮细胞都释放相似的自分泌生长因子,但它们对这些因子的反应取决于它们在体内的来源。体外睾酮刺激胡须细胞而非头皮细胞分泌一种自分泌生长因子,只有胡须细胞能够对其作出反应,这反映了体内对雄激素的反应。这些因子可能参与了雄激素诱导毛发大小变化所需的真皮乳头大小的关键增加。