Gu Y, Soares M J, Srivastava R K, Gibori G
Department of Physiology and Biophysics, University of Illinois, Chicago 60612-7342.
Endocrinology. 1994 Oct;135(4):1422-7. doi: 10.1210/endo.135.4.7925104.
It is well established that rat decidual tissue produces a PRL-like hormone(s) that binds to the PRL receptor on both the corpus luteum and the decidual cells and initiates profound changes in the endocrine milieu required for the establishment of pregnancy. The recent cloning of a decidual PRL-related protein (dPRP) prompted us 1) to determine whether the expression of this gene is triggered by decidualization of the endometrial stromal cells, 2) to examine the temporal and cell-specific pattern of its expression, and 3) to examine the role of both decidual signals and PRL on levels of its messenger RNA (mRNA). Total RNA was isolated from uteri of either nonpseudopregnant rats or pseudopregnant rats with or without decidual tissue. A 1-kilobase mRNA species hybridizing strongly with the dPRP probe was present in decidualized uteri. No dPRP mRNA could be detected in uteri not subjected to decidualization. Developmental studies indicated a constant high level of dPRP mRNA in the decidual tissue until day 12 of pseudopregnancy, followed by a marked decline at a time when extensive cell death occurs in the decidua, suggesting that dPRP is constitutively expressed in this tissue. To examine the cell-specific expression of dPRP, antimesometrial decidua was separated from mesometrial decidua, and the large antimesometrial cell population was separated from the small mesometrial cells by elutriation. The results of Northern analysis revealed clearly that dPRP is abundantly and solely expressed in the large antimesometrial cells. No dPRP mRNA could be detected in the mesometrial cells and in numerous other endocrine and nonendocrine tissues. A faint signal was observed, however, in the trophoblast. Despite the very strong paracrine regulation between the antimesometrial and mesometrial cells and the high levels of PRL receptor expression in these cells, both in vivo and coculture experiments revealed no regulation of dPRP gene expression by either PRL or mesometrial cell signal, adding further support to the possibility that once induced, dPRP remains constitutively expressed. In summary, the results of this investigation revealed that the expression of dPRP in endometrial stromal cells is triggered by the induction of decidualization and that this gene is selectively and abundantly expressed in a defined cell population located in the anti-mesometrial region of the uterus. Thus, dPRP is not only a useful indicator of decidualization, but is also an excellent marker for the differentiated antimesometrial cells.
众所周知,大鼠蜕膜组织会产生一种催乳素样激素,该激素可与黄体和蜕膜细胞上的催乳素受体结合,并引发建立妊娠所需的内分泌环境的深刻变化。最近克隆出的一种蜕膜催乳素相关蛋白(dPRP)促使我们:1)确定该基因的表达是否由子宫内膜基质细胞的蜕膜化触发;2)检查其表达的时间和细胞特异性模式;3)研究蜕膜信号和催乳素对其信使核糖核酸(mRNA)水平的作用。从非假孕大鼠或有或无蜕膜组织的假孕大鼠子宫中分离出总RNA。在蜕膜化的子宫中存在一种与dPRP探针强烈杂交的1千碱基mRNA种类。在未进行蜕膜化处理的子宫中未检测到dPRP mRNA。发育研究表明,在假孕第12天之前,蜕膜组织中dPRP mRNA水平持续较高,随后在蜕膜发生广泛细胞死亡时显著下降,这表明dPRP在该组织中是组成性表达的。为了检查dPRP的细胞特异性表达,将子宫系膜对侧蜕膜与子宫系膜侧蜕膜分离,并通过淘洗将子宫系膜对侧的大细胞群体与子宫系膜侧的小细胞分离。Northern分析结果清楚地显示,dPRP仅在子宫系膜对侧的大细胞中大量表达。在子宫系膜侧细胞以及许多其他内分泌和非内分泌组织中均未检测到dPRP mRNA。然而,在滋养层中观察到微弱信号。尽管子宫系膜对侧和子宫系膜侧细胞之间存在非常强的旁分泌调节,且这些细胞中催乳素受体表达水平较高,但体内和共培养实验均表明,PRL或子宫系膜侧细胞信号均未对dPRP基因表达产生调节作用,这进一步支持了dPRP一旦被诱导就持续组成性表达的可能性。总之,本研究结果表明,子宫内膜基质细胞中dPRP的表达由蜕膜化诱导触发,且该基因在位于子宫系膜对侧区域的特定细胞群体中选择性大量表达。因此,dPRP不仅是蜕膜化的有用指标,也是分化的子宫系膜对侧细胞的优良标志物。