Liver X receptor-α/βexpression ratio is increased in ACTH-secreting pituitary adenomas

Liver X receptor-α/βexpression ratio is increased in ACTH-secreting pituitary adenomas
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分泌 ACTH 的垂体腺瘤中肝脏 X 受体-α/β 表达比增加

DOI:
10.1016/j.neulet.2011.02.048
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发表时间:
2011
期刊:
影响因子:
2.5
通讯作者:
Mori M
Mori M
中科院分区:
医学4区
文献类型:
--
作者:
Hashimoto K;Matsumoto S;Ishida E;Miura A;Horiguchi K;Ozawa A;Shibusawa N;Satoh T;Yamada M;Yamada S;Mori M

文献摘要

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肝脏 X 受体(LXR-α 和 -β)是核氧甾醇受体,在调节胆固醇转运和代谢相关基因的表达中发挥关键作用。最近,一些研究小组报告说 LXR 还可以调节肾上腺类固醇生成。在之前的报告中,我们证明了LXR-α在垂体中显性表达,并且LXR-α在转录水平正向调节阿片黑皮素原(POMC)基因启动子。在本报告中,我们评估了人垂体瘤中LXR-α和-β基因的表达水平。尽管ACTH分泌腺瘤中LXR-α mRNA水平没有显着增加,但LXR-α/β表达比显着高于包括正常垂体在内的其他垂体肿瘤。此外,在表达POMC基因的At-T20细胞中,LXR-β的过度表达降低了POMC基因启动子活性。因此,我们得出结论,LXR-α/β基因表达比是激活分泌ACTH的垂体腺瘤中POMC基因表达的关键因素。
The liver X receptors (LXR-α and -β) are nuclear oxysterol receptors that play pivotal roles in regulating the expression of genes involved in cholesterol transport and metabolism. Recently, several groups have reported that the LXRs also regulate adrenal steroidogenesis. In the previous report, we demonstrated that LXR-α is dominantly expressed in the pituitary and that LXR-α positively regulates the proopiomelanocortin (POMC) gene promoter at the transcriptional level. In this report, we evaluated the expression levels of LXR-α and -β gene in the human pituitary tumor. Even though LXR-α mRNA levels are not significantly increased in ACTH-secreting adenomas, LXR-α/β expression ratio is significantly higher than other pituitary tumors including normal pituitaries. Furthermore, in At-T20 cells, which express POMC gene, overexpression of LXR-β decreased POMC gene promoter activities. Thus, we concluded that LXR-α/β gene expression ratio is a critical factor to activate POMC gene expression in ACTH-secreting pituitary adenomas.