Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor
Identification of murine uterine genes regulated in a ligand-dependent manner by the progesterone receptor
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DOI：
10.1210/en.2005-0016
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发表时间：
2005-08-01
期刊：
影响因子：
4.8
通讯作者：
DeMayo, FJ
中科院分区：
文献类型：
--
作者：
Jeong, JW;Lee, KY;DeMayo, FJ
孕酮（P4）通过其同源受体孕酮受体（PR）在子宫生理中起重要作用。PR敲除（PRKO）小鼠已经证明了P4-PR轴在调节子宫功能中的重要性。为了明确P4- pr在小鼠子宫中调控的分子通路，我们使用Affymetrix MG U74Av2寡核苷酸阵列来鉴定急性和慢性P4治疗后基因表达的变化。PRKO和野生型小鼠分别切除卵巢，然后每12 h注射1 mg P4，第一次注射P4（急性P4治疗）后4 h或第四次注射P4（慢性P4治疗）后4 h杀死小鼠。在基因组水平上，急性P4治疗后基因表达的主要变化是55个基因的表达增加。相反，慢性P4治疗后基因表达的主要变化是102个基因表达的总体降低。分析维甲酸代谢基因、细胞色素p450 26a1 （Cyp26a1）、醇脱氢酶5、醛脱氢酶1a1 (Aldh1a1)；kallikrein基因Klk5和Klk6；特异性转录因子GATA-2和Cited2 [camp -皮质酮结合蛋白/p300与谷氨酸(E)和天冬氨酸(D)-富尾相互作用的反激活因子]被证实受P4-PR轴调控。鉴定和分析这些应答基因将有助于明确PR在调节子宫生物学中的作用。
Progesterone (P4) acting through its cognate receptor, the progesterone receptor ( PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. PRKO and wild-type mice were ovariectomized and then treated with vehicle or 1 mg P4 every 12 h. Mice were killed either 4 h after the first injection ( acute P4 treatment) or after the fourth injection of P4 ( chronic P4 treatment). At the genomic level, the major change in gene expression after acute P4 treatment was an increase in the expression of 55 genes. Conversely, the major change in gene expression after chronic P4 treatment was an overall reduction in the expression of 102 genes. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 ( Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid ( E) and aspartic acid ( D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.