Reis F M, Luisi S, Florio P, Degrassi A, Petraglia F
University of Siena, Siena, Italy.
Placenta. 2002 Jul;23(6):522-5. doi: 10.1053/plac.2002.0831.
Human placenta produces activin A, a glycoprotein belonging to the transforming growth factor beta superfamily, which modulates several placental immune and endocrine functions. However, substances involved in controlling placental activin A production are not yet completely elucidated. The aim of the present study was to investigate the effects of placental products, corticotropin-releasing factor (CRF), urocortin, prostaglandin E(2) (PGE(2)) and endothelin-1 (ET-1) on activin A release from cultured human placental cells. Placental tissue was collected at term from normal pregnancies and a trophoblast-enriched cell preparation was cultured for 48 h. The test substances were applied (concentration from 10(-9)-10(-7)M) and the medium was harvested after 3 h incubation; vehicle-treated cells (controls) were present in each experiment. Activin A concentrations in culture medium were measured by using a specific two-site enzyme immunoassay. The addition of CRF resulted in a dose-related increase of activin A concentrations (P < 0.01). The stimulatory effect of CRF was significantly reversed by alpha-helical CRF(9-41), the CRF receptor antagonist. Urocortin showed a stimulating effect on activin A release from placental cells (P < 0.05) but not dose-related; the effect of urocortin was reversed by an equimolar dose of CRF antagonist, astressin. ET-1 significantly increased activin A concentrations in the culture medium only at the highest concentration, 10(-7)M (P < 0.05). No difference in activin A release was observed after incubating the cells with PGE(2). The evidence that CRF, urocortin and ET-1 stimulate activin A secretion from cultured placental cells suggests that these vasoactive factors may affect the changes of placental activin A secretion in pre-eclamptic woman.
人胎盘可产生激活素A,这是一种属于转化生长因子β超家族的糖蛋白,它可调节多种胎盘免疫和内分泌功能。然而,参与控制胎盘激活素A产生的物质尚未完全阐明。本研究的目的是探讨胎盘产物、促肾上腺皮质激素释放因子(CRF)、尿皮质素、前列腺素E2(PGE2)和内皮素-1(ET-1)对培养的人胎盘细胞释放激活素A的影响。足月时从正常妊娠中收集胎盘组织,并将富含滋养层的细胞制剂培养48小时。应用测试物质(浓度为10-9 - 10-7M),孵育3小时后收集培养基;每个实验均设置了用溶剂处理的细胞(对照)。通过使用特异性双位点酶免疫测定法测量培养基中激活素A的浓度。添加CRF导致激活素A浓度呈剂量相关增加(P < 0.01)。CRF受体拮抗剂α-螺旋CRF(9-41)可显著逆转CRF的刺激作用。尿皮质素对胎盘细胞释放激活素A有刺激作用(P < 0.05),但与剂量无关;等摩尔剂量的CRF拮抗剂阿斯特辛可逆转尿皮质素的作用。ET-1仅在最高浓度10-7M时显著增加培养基中激活素A的浓度(P < 0.05)。用PGE2孵育细胞后,未观察到激活素A释放的差异。CRF、尿皮质素和ET-1刺激培养的胎盘细胞分泌激活素A的证据表明,这些血管活性因子可能影响子痫前期妇女胎盘激活素A分泌的变化。