Increased transcription and increased messenger ribonucleic acid (mRNA) stability contribute to increased GATA6 mRNA abundance in polycystic ovary syndrome theca cells
Increased transcription and increased messenger ribonucleic acid (mRNA) stability contribute to increased GATA6 mRNA abundance in polycystic ovary syndrome theca cells
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DOI：
10.1210/jc.2005-0890
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发表时间：
2005-12-01
影响因子：
5.8
通讯作者：
Strauss, JF
中科院分区：
文献类型：
--
作者：
Ho, CKM;Wood, JR;Strauss, JF
背景：多囊卵巢综合征（PCOS）卵泡膜细胞分泌雄激素水平增加。在PCOS卵泡膜细胞中，调节几种类固醇生成酶表达的转录因子GATA 6的mRNA和蛋白水平增加。因此，GATA 6是PCOS的候选基因。目的：本研究的目的是探索PCOS卵泡膜细胞中GATA 6 mRNA水平增加的机制。设计：分别对正常个体和PCOS患者的卵泡膜细胞cDNA和基因组DNA进行定量RT-PCR和序列分析。设置：实验在大学实验室进行。参与者：469个家庭中至少有一个PCOS患者被确定为遗传研究。结果：PCOS卵泡膜细胞中反映GATA 6基因转录水平的新生GATA 6转录水平明显升高，而正常卵泡膜细胞中GATA 6转录水平明显升高。在正常卵泡膜细胞中，GATA 6 mRNA具有短的半衰期，这归因于富含AU的3 '-非翻译区序列。GATA 6转录物在PCOS卵泡膜细胞中的半衰期也显著延长。结论：在PCOS卵泡膜细胞中，GATA 6基因转录水平和mRNA稳定性增加。由于与PCOS相关的GATA 6基因位点没有序列变异，因此基因转录和mRNA稳定性的增加可能是由于PCOS卵泡膜细胞的内在差异。
Context: Polycystic ovary syndrome ( PCOS) theca cells secrete increased levels of androgens. The mRNA and protein levels of the transcription factor GATA6, which regulates expression of several steroidogenic enzymes, are increased in PCOS theca cells. Thus, GATA6 is a PCOS candidate gene.Objective: The objective of the study was to explore mechanisms by which GATA6 mRNA levels are increased in PCOS theca cells.Design: Theca cell cDNA and genomic DNA from normal individuals and PCOS patients were subjected to quantitative RT-PCR and sequence analysis, respectively.Setting: The experiments were performed in a university laboratory.Participants: Four hundred sixty-nine families that contain at least one PCOS patient were ascertained for genetic studies. Theca cells were obtained from four normal individuals and four PCOS patients.Results: Nascent GATA6 transcript levels, which reflect GATA6 gene transcription, were significantly increased in PCOS theca cells. In normal theca cells, GATA6 mRNA has a short half-life, which was attributed to an AU-rich 3'-untranslated region sequence. The half-life of GATA6 transcripts was also significantly longer in the PCOS theca cells. However, no sequence variations in the GATA6 gene locus were associated with PCOS.Conclusions: In PCOS theca cells, GATA6 gene transcription and the stability of the GATA6 mRNA are increased. Because there is no sequence variation in the GATA6 gene locus, which is associated with PCOS, it is likely that the increased gene transcription and mRNA stability are due to intrinsic differences in PCOS theca cells.