Photoperiod and testosterone modulate growth and melanogenesis of S91 murine melanoma

Photoperiod and testosterone modulate growth and melanogenesis of S91 murine melanoma
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DOI:
10.2174/157340608783789185
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发表时间:
2008-03-01
影响因子:
2.3
通讯作者:
Isoldi, Mauro C.
Isoldi, Mauro C.
中科院分区:
医学4区
文献类型:
--
作者:
Allil, Paulo A. A.;Visconti, Maria A.;Isoldi, Mauro C.

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用S91鼠黑素瘤细胞进行体内和体外测定,旨在研究睾酮和光周期对肿瘤生长和黑素生成(酪氨酸酶活性)的影响。通过在接受递增浓度睾酮并接受不同光周期方案的去势小鼠中诱导黑色素瘤进行体内测定。结果表明,在接受最长日照的动物中,黑色素含量的增加更高,从而证明了光周期长度在黑色素合成中的重要性。在提交至12 L:12 D的睾酮治疗动物中观察到肿瘤生长和蛋白质含量增加;在提交至4 L:20 D和20 L:4 D的睾酮治疗动物中,肿瘤生长显著较小。在S91培养细胞中,睾酮以剂量依赖性方式增加细胞增殖并降低酪氨酸酶活性。放射性结合试验表明,激素通过低亲和力睾酮受体起作用,因为芳香酶抑制剂的存在不会以统计学显著的方式影响结合试验,并且所有体外实验都是在抑制剂存在下进行的。我们的体内数据加上体外结果证实了S91黑色素瘤细胞直接响应睾酮的假设,这种作用是由光调制。
In vivo and in vitro assays were performed with S91 murine melanoma cells aiming to investigate the effects of testosterone and photoperiod on tumor growth and melanogenesis (tyrosinase activity). In vivo assays were performed by inducing melanoma tumors in castrated mice receiving increasing concentrations of testosterone and submitted to varying photoperiod regimens. The results demonstrated that the increase of melanin content was higher in animals submitted to the longest days, thus demonstrating the importance of photoperiod length in melanin synthesis. Increase in tumor growth and protein content was observed in testosterone-treated animals submitted to 12L:12D; in testosterone-treated animals submitted to 4L:20D and 20L:4D tumor growth was significantly smaller. In S91 cultured cells, testosterone increased cell proliferation and reduced tyrosinase activity in a dose-dependent manner. Radioactive binding assays demonstrated that the hormone was acting through low affinity testosterone receptors, since the presence of aromatase inhibitor did not affect the binding assay in a statistically significant way, and all the in vitro experiments were performed in the presence of the inhibitor. Our in vivo data added to the in vitro results corroborate the hypothesis that S91 melanoma cells directly respond to testosterone and that this effect is modulated by light.