Petraglia F, Sawchenko P E, Rivier J, Vale W
Nature. 1987;328(6132):717-9. doi: 10.1038/328717a0.
The hypothalamic-pituitary-adrenocortical axis is activated in pregnancy and parturition. Levels of immunoreactive corticotrophin releasing factor (irCRF), immunoreactive adrenocorticotropic hormone (irACTH) and cortisol concentrations in maternal plasma are elevated throughout gestation, increase further during labour and fall precipitously after parturition. The placenta contains biologically active CRF and ACTH and it has been suggested that the placenta produces these peptides during pregnancy. Here we show that irCRF is located in the cytotrophoblast cells of placenta collected at term. Using a monolayer primary culture of human placental cells we have found that CRF stimulates secretion of peptides containing the ACTH sequence in the placenta in a dose-dependent manner, as it does in the pituitary. This effect is reversed by a CRF antagonist and is mimicked by dibutyryl cyclic AMP and forskolin. Glucocorticoids, which suppress the secretion of pituitary ACTH, were found to have no influence on release of irACTH by the placenta. Oxytocin and prostaglandins stimulate irACTH and irCRF secretion from cultured placental cells and the irACTH-releasing activity of two prostaglandins is partially reversed by a CRF antagonist. Thus CRF may be involved in the paracrine regulation of placental irACTH secretion.
下丘脑 - 垂体 - 肾上腺皮质轴在妊娠和分娩过程中被激活。整个妊娠期母体血浆中免疫反应性促肾上腺皮质激素释放因子（irCRF）、免疫反应性促肾上腺皮质激素（irACTH）水平及皮质醇浓度均升高，分娩时进一步增加，产后急剧下降。胎盘含有生物活性的CRF和ACTH，有人提出胎盘在孕期产生这些肽类物质。在此我们表明，irCRF位于足月收集的胎盘细胞滋养层细胞中。利用人胎盘细胞的单层原代培养，我们发现CRF能像在垂体中一样，以剂量依赖的方式刺激胎盘中含有ACTH序列的肽类物质分泌。这种作用可被CRF拮抗剂逆转，且二丁酰环磷腺苷和福斯可林可模拟此作用。糖皮质激素可抑制垂体ACTH的分泌，但对胎盘释放irACTH没有影响。催产素和前列腺素可刺激培养的胎盘细胞分泌irACTH和irCRF，两种前列腺素的irACTH释放活性可被CRF拮抗剂部分逆转。因此，CRF可能参与胎盘irACTH分泌的旁分泌调节。
