STIMULATION OF AROMATASE-ACTIVITY BY DIHYDROTESTOSTERONE IN HUMAN-SKIN FIBROBLASTS
STIMULATION OF AROMATASE-ACTIVITY BY DIHYDROTESTOSTERONE IN HUMAN-SKIN FIBROBLASTS
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DOI：
10.1016/0022-4731(86)90296-7
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发表时间：
1986-07-01
影响因子：
4.1
通讯作者：
DESCOMPS, B
中科院分区：
文献类型：
--
作者：
CHABAB, A;SULTAN, C;DESCOMPS, B
为了研究雄激素对正常青春期前男性生殖器皮肤成纤维细胞芳香酶活性的调节，在不同浓度的非芳香化雄激素DHT(5α-二氢睾酮)存在下，对培养的正常男性生殖器皮肤成纤维细胞芳香化酶活性进行了测定。细胞与10-6M雄烯二酮孵育24小时后，用酶法检测雌激素的生成。浓度为10-10和10-9M的DHT可使细胞芳香酶活性提高3~20倍。要实现这一刺激，需预先与细胞孵育48h。预培养24 h后，刺激作用不明显，芳香酶活性的基础值在8.+-范围内。1.2 pmol/mg蛋白质/天(平均值+-扫描电子显微镜)，最大刺激为1043.+-。当浓度为10-8M DHT时，每天可获得46pmoL/mg蛋白质。这种刺激可被20.+-水平的醋酸环丙孕酮部分阻断。4pmol/mg蛋白质/天；因此，DHT对芳香酶活性的刺激可能是由雄激素受体介导的。这种刺激作用可通过与放线菌素D或放线菌素D孵育细胞而被阻止，提示DHT通过诱导新的蛋白质物质的合成而提高培养的成纤维细胞中芳香化酶的活性。在体外，雄激素对芳香酶活性的调节可能为雌激素的腺外形成提供一种新的途径。
In order to study the regulation of aromatase activity by androgens in cultured fibroblasts derived from genital skin of normal prepubertal boys, aromatase activity was evaluated in the presence of various concentrations of non-aromatizable androgen DHT(5.alpha.-dihydrotestosterone). The estrogen formation was assayed by an enzymatic method, after 24 h incubation of the cells with 10-6 M androstenedione. Aromatase activity was stimulated 3- to 20-fold by DHT at concentrations 10-10 and 10-9 M. It was necessary to preincubate the cells with DHT for 48 h in order to bring about this stimulation. The stimulatory effect was not significant after preincubation for only 24 h. The basal value of aromatase activity was in range of 8 .+-. 1.2 pmol/mg protein/day (mean .+-. SEM), while the maximal stimulation 1043 .+-. 46 pmol/mg protein/day was obtained at the concentration of 10-8 M DHT. This stimulation was partially blocked with cyproterone acetate at level of 20 .+-. 4 pmol/mg protein/day; stimulation of aromatase activity by DHT could thus be mediated by the androgen receptor. This stimulatory effect was prevented by incubation of the cells with cycloheximide or actinomycin D, suggesting that DHT acts to increase aromatase activity in cultured fibroblasts by inducing the synthesis of new proteinaceous material. In vitro regulation of aromatase activity by androgens could contribute to a new approach to the extraglandular formation of estrogen.