Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo.
Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo.
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源自人毛囊的培养真皮乳头细胞中雄激素作用机制，体内对雄激素有不同的反应。
DOI：
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发表时间：
1992
影响因子：
6.5
通讯作者：
A. Messenger
中科院分区：
文献类型：
--
作者：
V. Randall;M. Thornton;K. Hamada;A. Messenger
雄激素是人类头发生长的主要调节因素，但它们的影响各不相同：许多毛囊受到雄激素的刺激，如胡须；一些毛囊不受影响，如睫毛；而遗传个体的头皮毛囊经历退化和秃顶。由于毛乳头控制毛囊的许多方面，雄激素可能通过毛乳头起作用，间接影响毛囊的其他成分。在这一假说中，雄激素会改变毛乳头细胞产生的调节物质，例如生长因子和/或细胞外基质成分。为了验证这一理论，我们在雄激素依赖毛囊和相对雄激素非依赖性非秃顶头皮培养的毛乳头细胞原代系中比较了雄激素的作用机制。用合成的雄激素[~3H]-米博洛酮进行饱和分析(9~10点；0.05~10nmol/L)测定雄激素受体水平，并通过竞争性研究证实特异性。用5 NM[3 H]-睾酮孵育2 h后，观察细胞内和培养液中雄激素代谢的变化。在提取液中加入载体和[14C]类固醇，然后用薄层层析分离；重结晶确认类固醇的同一性。来自雄激素依赖毛囊的毛乳头细胞比非秃顶的头皮细胞含有更高水平的特异性、高亲和力、低容量的雄激素受体。胡须、公共和头皮细胞的睾酮代谢也不同，细胞内含有睾酮和雄烯二酮，但只有胡须细胞产生5α-二氢睾酮，这与5α-还原酶缺乏症中发现的稀疏胡须生长一致。在其他地方，我们已经证明了培养的毛乳头细胞产生细胞外基质成分和有丝分裂因子。这些结果都与我们最初的假设一致，并表明对这类细胞的进一步研究可能会阐明雄激素对人类毛囊的矛盾影响。
Androgens are major regulators of human hair growth, but their effects vary: many follicles are stimulated by androgens, e.g., beard; some remain unaffected, e.g., eyelashes; whereas scalp follicles undergo regression and balding in genetically disposed individuals. Because the dermal papilla controls many aspects of the hair follicle, androgens may act via the dermal papilla, affecting the other follicular components indirectly. In this hypothesis androgens would alter dermal papilla cell production of regulatory substances, e.g., growth factors and/or extracellular matrix components. To test this theory the mechanism of androgen action has been compared in primary lines of dermal papilla cells cultured from androgen-dependent follicles and relatively androgen-independent non-balding scalp. Androgen receptor levels were assayed by saturation analysis (9-10 points; 0.05-10 nmol/l) using the synthetic androgen [3H]-mibolerone and specificity was confirmed by competition studies. Androgen metabolism was investigated both intracellularly and in the media after a 2-h incubation with 5 nM [3H]-testosterone. Carrier and [14C] steroids were added to the extracts before separation by thin-layer chromatography; steroid identity was confirmed by recrystallization. Dermal papilla cells from androgen-dependent follicles contained higher levels of specific, high-affinity, low-capacity androgen receptors than non-balding scalp cells. Testosterone metabolism also varied with beard, public and scalp cells containing testosterone and androstenedione intracellularly, but only beard cells producing 5 alpha-dihydrotestosterone, in line with the scanty beard growth found in 5 alpha-reductase deficiency. Elsewhere we have shown that cultured dermal papilla cells produce extracellular matrix components and mitogenic factors. These results all concur with our original hypothesis and suggest that further studies of such cells may elucidate the paradoxical effects of androgens on human hair follicles.
雄激素受体的分子缺陷导致雄激素抵抗。
DOI：
10.1111/1523-1747.ep12462322
发表时间：
1992
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
McPhaul,MJ;Marcelli,M
通讯作者：
Marcelli,M
DOI：
10.1002/9780470720899.ch12
发表时间：
1984
期刊：
Ciba Foundation symposium
影响因子：
--
作者：
Bernfield,M;Banerjee,SD;Koda,JE;Rapraeger,AC
通讯作者：
Rapraeger,AC
研究培养的毛发和皮肤细胞中的雄激素代谢和作用。
DOI：
10.1016/0022-4731(86)90359-6
发表时间：
1986
期刊：
Journal of steroid biochemistry
影响因子：
--
作者：
Maudelonde,T;Rosenfield,RL;Shuler,CF;Schwartz,SA
通讯作者：
Schwartz,SA