Inhibitory effects of TNFα on mouse tumor Leydig cells:: possible role of ceramide in the mechanism of action
Inhibitory effects of TNFα on mouse tumor Leydig cells:: possible role of ceramide in the mechanism of action
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DOI：
10.1016/s0303-7207(99)00029-5
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发表时间：
1999-04-25
影响因子：
4.1
通讯作者：
Mukhopadhyay, AK
中科院分区：
文献类型：
--
作者：
Budnik, LT;Jähner, D;Mukhopadhyay, AK
据报道，TNF α抑制小鼠Leydig细胞中的类固醇生成。在原代细胞中，这种抑制主要是由于Cyp-17基因表达的减少。小鼠肿瘤Leydig细胞，MA-IO，不含巨噬细胞且缺乏Cyp-17，似乎是研究TNF α不依赖于巨噬细胞或Cyp-17的那些作用的极好模型。我们在这里报告了TNF α受体在该细胞系中表达。用TNF α处理细胞对基础孕酮产生没有影响。与此相反，LH-，8Br-cAMP和毛喉素刺激的孕酮的生产被TNF α抑制。参与胆固醇转化为双烯醇酮的酶和双烯醇酮诱导的[C-14]胆固醇酯水解均不受TNF α的影响。激素诱导的星星蛋白表达在TNF α处理的细胞的线粒体组分中减少。此外，细胞渗透性神经酰胺显着抑制星星蛋白水平。我们进一步表明，TNF α能够诱导[C-14]-神经酰胺在MA-10细胞中的积累，并表明这种鞘脂可以被认为是TNF α信号的传递给星星蛋白。(C)1999爱思唯尔科学爱尔兰有限公司保留所有权利。
TNF alpha is reported to inhibit steroidogenesis in mouse Leydig cells. In primary cells this inhibition resulted mainly from a reduced expression of Cyp-17 gene. Mouse tumor Leydig cells, MA-IO, being free of macrophages and lacking Cyp-17, appear to be an excellent model to investigate those effects of TNFa which are independent of either macrophages or Cyp-17. We report here that TNF alpha receptors are expressed in this cell line. Treatment of the cells with TNF alpha had no effect on basal progesterone production. In contrast, LH-, 8Br-cAMP and forskolin-stimulated progesterone production was inhibited by TNF alpha. Neither enzymes involved in the conversion of cholesterol to pregnenolone nor hormone-induced hydrolysis of [C-14] cholesterol-ester were affected by TNF alpha. The hormone- induced expression of StAR protein was diminished in mitochondrial fractions from TNF alpha-treated cells. Also cell permeable ceramides markedly inhibited StAR protein levels. We show further that TNF alpha was able to induce [C-14]-ceramide accumulation in MA-10 cells and suggest that this sphingolipid may be considered as a transmitter of TNF alpha signals to the StAR protein. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.