Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro
Regulated expression of signal transducer and activator of transcription, Stat5, and its enhancement of PRL expression in human endometrial stromal cells in vitro
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DOI：
10.1210/jc.87.6.2581
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发表时间：
2002-06-01
影响因子：
5.8
通讯作者：
White, JO
中科院分区：
文献类型：
--
作者：
Mak, IYH;Brosens, JJ;White, JO
人子宫内膜在月经周期的分泌期的分化的特征在于参与妊娠的建立和维持的多种基因的表达。在分泌期大量的信号转导子和转录激活子（Stats）表明Stat 5是体内子宫内膜对卵巢激素刺激反应的分化的一个组成部分。子宫内膜间质细胞（ESC）在体内分泌期的一个亚群中开始蜕膜化，但目前尚不清楚Stat 5的表达是否受调控是这些细胞的特征。因此，在这里，Stat 5在ESC中的丰度和亚细胞分布后，蜕膜化刺激的cAMP加醋酸甲羟孕酮（MPA）已在体外研究。Western blotting显示，在刺激后2，3和4 d，Stat 5a和Stat 5 b的表观丰度在胞质和核组分中增加。瞬时转染的Stat 5a或Stat 5 b显著增强蜕膜PRL启动子对cAMP/MPA的反应和显性负性Stat 5对cAMP/MPA的反应的减弱的能力表明Stat 5增加的潜在功能相关性。最近的证据表明，子宫内膜分化，包括PRL的生产，作为一个可能的目标抗磷脂抗体（aPL）的流行在复发性流产。与人aPL具有相似反应性的单克隆抗体ID 2显著降低了细胞核Stat 5 b对cAMP/MPA的反应的表观丰度，并与蜕膜PRL启动子活化和PRL分泌降低相关。因此，Stat 5的调节表达是人ESC蜕膜分化的一个组成部分，并显著促进蜕膜PRL启动子的激活。通过aPL组分改变这一过程表明，蜕膜分化是复发性早期流产的潜在临床靶点。
Differentiation of human endometrium during the secretory phase of the menstrual cycle is characterized by expression of a variety of genes implicated in the establishment and maintenance of pregnancy. An increased abundance of signal transducers and activators of transcription (Stats) in the secretory phase suggests Stat5 as a component of the differentiation of endometrium in response to ovarian hormone stimulation in vivo. Decidualization is initiated in a subset of endometrial stromal cells (ESC) in vivo during the secretory phase, but it is unclear whether regulated expression of Stat5 is a feature of these cells. Here, therefore, the abundance and subcellular distribution of Stat5 in ESC after a decidualization stimulus of cAMP plus medroxyprogesterone acetate (MPA) has been investigated in vitro. Western blotting revealed an increase in the apparent abundance of Stat5a and Stat5b, in the cytosolic and nuclear fractions, at 2, 3, and 4 d after stimulation. The potential functional relevance of this increase in Stat5 is suggested by the ability of transiently transfected Stat5a or Stat5b to significantly enhance the response of the decidual PRL promoter to cAMP/MPA and attenuation of the response to CAMP/MPA by dominant negative Stat5. Recent evidence suggests endometrial differentiation, including PRL production, as a possible target of antiphospholipid antibodies (aPL) prevalent in recurrent miscarriage. Monoclonal antibody, ID2, which has similar reactivity as human aPL, significantly decreased the apparent abundance of nuclear Stat5b in response to cAMP/MPA and was associated with decreased decidual PRL promoter activation and PRL secretion. Regulated expression of Stat5 is therefore a component of decidual differentiation of human ESC and contributes significantly to activation of the decidual PRL promoter. Alteration of this process by an aPL component suggests decidual differentiation as a potential clinical target in recurrent early miscarriages.