Gu Y, Srivastava R K, Ou J, Krett N L, Mayo K E, Gibori G
Department of Physiology and Biophysics, University of Illinois College of Medicine, Chicago 60612, USA.
Endocrinology. 1995 Sep;136(9):3815-22. doi: 10.1210/endo.136.9.7544272.
Rat decidual tissue is formed by two distinct decidual cell populations located either antimesometrially or mesometrially in the uterus. They differ in morphology, the genes they express, the proteins they secrete, and the role they play during pregnancy. Recently, we have shown that rat decidua expresses follistatin and alpha 2-macroglobulin (alpha 2-MG), two binding proteins to activin. In the present study, we determined whether the decidua of pregnant and pseudopregnant rats also expresses activin, whether activin messenger RNA (mRNA) is confined to a particular cell population, and whether it is regulated by its binding proteins. Decidual and placental tissues were collected at different stages of pseudopregnancy or pregnancy. mRNA expression was examined by in situ hybridization, reverse transcription-polymerase chain reaction, and Northern analysis. Developmental studies revealed that activin A became highly expressed in the antimesometrial decidua only from day 11 at a time when this tissue was undergoing extensive degeneration. Very little activin A mRNA could be detected in the mesometrial decidua. However, late in pregnancy, significant expression of activin A mRNA was detected in the mesometrial decidua undergoing extensive cell death at this stage. Developmental study revealed that activin A mRNA became expressed in the antimesometrial decidua only when follistatin mRNA disappeared from this tissue. Furthermore, mesometrial decidua expressing the most alpha 2-MG mRNA had reduced levels of activin A mRNA. These data suggest that follistatin and alpha 2-MG may, by binding to activin, prevent activin A from stimulating the expression of its own gene. To examine this possibility we first established that the rat decidua expresses activin receptor II at a constant level between days 11-15. Then we examined whether follistatin and alpha 2-MG down-regulate activin expression in a simian virus 40-transformed decidual cell line (GG-AD). These cells express activin A mRNA in abundance, very little follistatin, and no alpha 2-MG. Follistatin and alpha 2-MG caused a dose-related decrease in activin A mRNA levels in these cells. The same inhibitory effect was observed with activin A-blocking antibody. In summary, the results of this investigation demonstrate that rat decidual tissue expresses mRNAs for activin A and its two binding proteins; follistatin and alpha 2-MG. The expression of each mRNA is cell specific and developmentally regulated. The finding that both activin-binding proteins and antibody inhibit the expression of activin A in cultured decidual cells suggests that activin regulates its own gene expression in the decidua.(ABSTRACT TRUNCATED AT 400 WORDS)
大鼠蜕膜组织由子宫中位于反系膜侧或系膜侧的两种不同的蜕膜细胞群体组成。它们在形态、表达的基因、分泌的蛋白质以及在妊娠期间所起的作用方面存在差异。最近，我们发现大鼠蜕膜表达卵泡抑素和α2-巨球蛋白（α2-MG），这两种都是激活素的结合蛋白。在本研究中，我们确定妊娠和假孕大鼠的蜕膜是否也表达激活素，激活素信使核糖核酸（mRNA）是否局限于特定的细胞群体，以及它是否受其结合蛋白的调节。在假孕或妊娠的不同阶段收集蜕膜和胎盘组织。通过原位杂交、逆转录-聚合酶链反应和Northern分析检测mRNA表达。发育研究表明，激活素A仅在第11天开始在反系膜侧蜕膜中高度表达，此时该组织正在经历广泛的退化。在系膜侧蜕膜中几乎检测不到激活素A mRNA。然而，在妊娠后期，在此时正在经历广泛细胞死亡的系膜侧蜕膜中检测到激活素A mRNA的显著表达。发育研究表明，激活素A mRNA仅在卵泡抑素mRNA从该组织中消失时才在反系膜侧蜕膜中表达。此外，表达最多α2-MG mRNA的系膜侧蜕膜中激活素A mRNA水平降低。这些数据表明，卵泡抑素和α2-MG可能通过与激活素结合，阻止激活素A刺激其自身基因的表达。为了检验这种可能性，我们首先确定大鼠蜕膜在第11至15天之间以恒定水平表达激活素受体II。然后我们研究卵泡抑素和α2-MG是否下调猿猴病毒40转化的蜕膜细胞系（GG-AD）中的激活素表达。这些细胞大量表达激活素A mRNA，很少表达卵泡抑素，不表达α2-MG。卵泡抑素和α2-MG导致这些细胞中激活素A mRNA水平呈剂量相关下降。用激活素A阻断抗体也观察到相同的抑制作用。总之，本研究结果表明大鼠蜕膜组织表达激活素A及其两种结合蛋白卵泡抑素和α2-MG的mRNA。每种mRNA的表达具有细胞特异性并受发育调节。激活素结合蛋白和抗体均抑制培养的蜕膜细胞中激活素A的表达这一发现表明，激活素在蜕膜中调节其自身的基因表达。（摘要截短至400字）
