Guller S, Markiewicz L, Wozniak R, Burnham J M, Wang E Y, Kaplan P, Lockwood C J
Department of Obstetrics/Gynecology and Reproductive Science, Mt. Sinai Medical Center, New York, New York 10029.
Endocrinology. 1994 May;134(5):2064-71. doi: 10.1210/endo.134.5.8156906.
The extracellular matrix (ECM) protein fibronectin (FN) is a critical regulator of uterine-placental adherence. In the present report we compared the effects of glucocorticoids on FN expression in cytotrophoblast cultures isolated from human first trimester and term placentas to elucidate potential steroid-dependent cellular mechanisms associated with human parturition. Based on immunoassays, treatment of first trimester cytotrophoblasts with 10(-7) M dexamethasone (DEX) for 2 cr 4 days reduced medium levels of oncofetal FN (onfFN; i.e. FNs bearing an oncofetal epitope) to approximately 80% of control levels. Conversely, treatment of cytotrophoblasts isolated from term placentas with DEX dramatically reduced medium levels of onfFN to approximately 12% of control values. Treatment of both first trimester and term cells with 10(-6) M progestin, mineralocorticoid, or estrogen had no significant effect on onfFN expression in either cell type. Glucocorticoids specifically down-regulated medium levels of onfFN in term cells, but not in first trimester cells. In contrast, DEX treatment promoted an approximately 3- to 7-fold increase in levels of hCG in both first trimester and term cytotrophoblasts, suggesting that the effects of glucocorticoid on FN and hCG expression are elicited through independent cell-signaling pathways. In first trimester cells, DEX promoted a reduction in rates of FN and laminin synthesis to 60-70% of control levels. In term cells, DEX treatment reduced levels of FN and laminin synthesis to approximately 10% of control levels. Similarly, DEX treatment down-regulated levels of FN mRNA to approximately 60% and 10% of control values in first trimester and term cells, respectively. The first trimester of human pregnancy is associated with low levels of glucocorticoids and reduced glucocorticoid responsiveness. These conditions would favor high levels of placental ECM protein synthesis, thus stabilizing uterine-placental adherence. Conversely, elevated levels of glucocorticoids near parturition and increased glucocorticoid responsiveness would inhibit placental ECM protein synthesis, reducing uterine-placental adherence and promoting the separation of placenta from uterus.
细胞外基质（ECM）蛋白纤连蛋白（FN）是子宫 - 胎盘黏附的关键调节因子。在本报告中，我们比较了糖皮质激素对从人孕早期和足月胎盘分离的细胞滋养层细胞中FN表达的影响，以阐明与人类分娩相关的潜在类固醇依赖性细胞机制。基于免疫测定，用10（-7）M地塞米松（DEX）处理孕早期细胞滋养层细胞2或4天，可使癌胚FN（onfFN；即带有癌胚表位的FN）的培养基水平降至对照水平的约80％。相反，用DEX处理从足月胎盘分离的细胞滋养层细胞，可使onfFN的培养基水平大幅降至对照值的约12％。用10（-6）M孕激素、盐皮质激素或雌激素处理孕早期和足月细胞，对两种细胞类型中onfFN的表达均无显著影响。糖皮质激素特异性下调足月细胞中onfFN的培养基水平，但对孕早期细胞无此作用。相比之下，DEX处理促进孕早期和足月细胞滋养层细胞中hCG水平升高约3至7倍，表明糖皮质激素对FN和hCG表达的影响是通过独立的细胞信号通路引发的。在孕早期细胞中，DEX促进FN和层粘连蛋白合成速率降至对照水平的60 - 70％。在足月细胞中，DEX处理使FN和层粘连蛋白合成水平降至对照水平的约10％。同样，DEX处理分别将孕早期和足月细胞中FN mRNA水平下调至对照值的约60％和10％。人类妊娠的第一个三月期与低水平的糖皮质激素和降低的糖皮质激素反应性有关。这些情况有利于高水平的胎盘ECM蛋白合成，从而稳定子宫 - 胎盘黏附。相反，分娩时糖皮质激素水平升高和糖皮质激素反应性增加会抑制胎盘ECM蛋白合成，减少子宫 - 胎盘黏附并促进胎盘与子宫分离。
