The decidual prolactin receptor and its regulation by decidua-derived factors
The decidual prolactin receptor and its regulation by decidua-derived factors
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DOI：
10.1210/en.137.11.4878
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发表时间：
1996-11-01
期刊：
影响因子：
4.8
通讯作者：
Gibori, G
中科院分区：
文献类型：
--
作者：
Gu, Y;Srivastava, RK;Gibori, G
大鼠子宫内膜间质的蜕膜化产生了两种不同的细胞群，位于子宫中的系膜或反系膜。我们以前已经表明，大鼠蜕膜是一种催乳素样激素的生产和行动的网站。在这项研究中，我们使用逆转录-PCR检测了是否以及哪种类型的PRL受体（PRL-R）信使RNA（mRNA）在蜕膜中表达，受体是否仅限于一个细胞群，结果表明，假孕大鼠子宫不表达PRL-受体，R和蜕膜化不会触发PRL-R mRNA的快速出现。在诱导蜕膜化后3天，长型PRL-R才首次表达。此后，短型（PRL-R（S））和长型（PRL-R（L））的mRNA在反系膜和系膜蜕膜中都可检测到，尽管PRL-R（L）mRNA比PRL-R（S）丰富得多。随着发育的进行，PRL-R mRNA减少，消失，特别是从反子宫系膜蜕膜，而子宫系膜蜕膜继续表达这种受体mRNA。在抗子宫内膜组织中，伴随着PRL-R的下调，是激活素A的相当突然的表达。相反，维持高水平PRL-R mRNA的子宫系膜组织表达很少的激活素A，但产生激活素结合蛋白α 2-巨球蛋白（α 2 MG）。为了确定激活素A和α（2）MG是否调节PRL-R表达，通过淘洗分离抗子宫系膜细胞和子宫系膜细胞，并在存在或不存在激活素A、α（2）MG或卵泡抑素的情况下培养。细胞分离后，两种细胞群均表达PRL-R，但不表达激活素A。在6小时内，激活素A的mRNA和蛋白成为高表达的系膜细胞，而PRL-R，mRNA变得检测不到。相反，激活素A mRNA在抗子宫内膜细胞中处于非常低的水平，并且在培养基中至少12 h内未检测到激活素A蛋白。在这些细胞中，PRL-R的mRNA仍然升高。在抗子宫系膜细胞中加入激活素A可引起PRL-R mRNA表达的显著下调，而在子宫系膜细胞中加入α 2 MG和卵泡抑素可防止PRL-R的消失。总之，本研究的结果表明：1）子宫内膜间质的蜕膜化诱导两种形式的PRL-R mRNA的出现; 2）在形成蜕膜的两个细胞群中显示PRL-R mRNA的差异表达; 3）确定这种差异表达是由于两种关键的蜕膜分子，激活素A和α（2）巨球蛋白;和4）证明激活素A可导致蜕膜细胞失去PRL-R，并且通过向培养物中加入两种激活素结合蛋白卵泡抑素和α（2）MG可防止蜕膜PRL-R的消失。
Decidualization of the endometrial stroma in the rat gives rise to two different cell populations, located either mesometrially or antimesometrially in the uterus. We have previously shown that the rat decidua is the site of production and action of a PRL-like hormone. In this investigation we examined, using reverse transcription-PCR, whether and which type of PRL receptor (PRL-R) messenger RNA (mRNA) is expressed in the decidua, whether the receptor is confined only to one cell population, and whether the PRL-R expression is regulated by decidua-derived factors.The results indicate that the uterus of pseudopregnant rats does not express the PRL-R and that decidualization does not trigger a rapid appearance of PRL-R mRNA. It is only 3 days after the induction of decidualization that the long form of the PRL-R was first expressed. Thereafter, mRNAs for both the short (PRL-R(S)) and the long (PRL-R(L) form became detectable in both antimesometrial and mesometrial decidua, although PRL-R(L) mRNA was much more abundant than PRL-R(S). As development proceeded, PRL-R mRNA decreased and disappeared specifically from the antimesometrial decidua, whereas the mesometrial decidua continued to express this receptor mRNA. Concomitant with down-regulation of the PRL-R in the antimesometrial tissue was a rather abrupt expression of activin A. In contrast, the mesometrial tissue that maintained high levels of PRL-R mRNA expressed little activin A, but produced an activin-binding protein, alpha(2)-macroglobulin (alpha(2)MG). To determine whether activin A and alpha(2)MG regulate PRL-R expression, antimesometrial and mesometrial cells were separated by elutriation and maintained in culture in the presence or absence of activin A, alpha(2)MG, or follistatin. Just after cell separation, both cell populations expressed PRL-R, but not activin A. Within 6 h, activin A mRNA and protein became highly expressed in the mesometrial cells, whereas PRL-R, mRNA became undetectable. In contrast, activin A mRNA was at very low levels in the antimesometrial cells, and no activin A protein could be detected in the medium for at least 12 h. In these cells PRL-R, mRNA remained elevated. Addition of activin A to antimesometrial cells caused a marked down-regulation of PRL-R, mRNA expression, whereas addition of alpha(2)MG and follistatin to mesometrial cells prevented the disappearance of PRL-R.In summary, the results of this investigation 1) indicate that decidualization of the endometrial stroma induces the appearance of both forms of the PRL-R mRNAs; 2) show differential expression of the PRL-R mRNA in the two-cell population forming the decidua; 3) establish that this differential expression is due to two key decidual molecules, activin A and alpha(2) macroglobulin; and 4) demonstrate that activin A can cause the decidual cells to lose the PRL-R and that the disappearance of the decidual PRL-R can be prevented by addition to the culture of two activin binding proteins, follistatin and alpha(2)MG.