Pedersen A M, Fulton S K, Porter L, Francis G L
Department of Pediatrics, Walter Reed Army Medical Center, Washington, DC 20307-5001, USA.
J Reprod Immunol. 1995 May;29(1):69-80. doi: 10.1016/0165-0378(95)00931-a.
Steroid hormones, produced by the placenta, appear to be critically important in maintaining the pregnancy of experimental animals and possibly humans. Previous studies in our laboratory have shown that macrophage-conditioned media, which are known to contain several cytokines including tumor necrosis factor-alpha (TNF-alpha), decreased the in vitro synthesis of progesterone (P) and increased the synthesis of estradiol (E2) by placental fragments. The present study was designed to further our understanding of the effect of cytokines on the synthesis of placental trophoblast hormones. The current study shows that TNF-alpha (1-20 ng/ml) decreases the in vitro synthesis of P and increases the synthesis of both E2 and human chorionic gonadotropin (hCG) by JEG-3 choriocarcinoma cells (a model for trophoblast hormone synthesis). The effects of TNF-alpha are independent of changes in formation of adenosine 3':5' cyclic-monophosphate, guanosine 3':5' cyclic-monophosphate, prostaglandin E2, and prostaglandin F2 alpha. However, the effect of TNF-alpha on P formation is blocked by cycloheximide (1 microgram/ml). These observations suggest TNF-alpha could have effects on placental hormone synthesis which might be important in the pathogenesis of both normal and preterm labor. At least some of these effects appear mediated through new protein synthesis.
胎盘产生的甾体激素在维持实验动物乃至人类的妊娠过程中似乎至关重要。我们实验室之前的研究表明，巨噬细胞条件培养基（已知其中含有多种细胞因子，包括肿瘤坏死因子-α（TNF-α））会降低胎盘碎片孕酮（P）的体外合成，并增加雌二醇（E2）的合成。本研究旨在进一步了解细胞因子对胎盘滋养层激素合成的影响。当前研究表明，TNF-α（1 - 20 ng/ml）可降低JEG-3绒毛膜癌细胞（一种滋养层激素合成模型）P的体外合成，并增加E2和人绒毛膜促性腺激素（hCG）的合成。TNF-α的作用与3':5'-环磷酸腺苷、3':5'-环磷酸鸟苷、前列腺素E2和前列腺素F2α生成的变化无关。然而，TNF-α对P生成的作用可被放线菌酮（1微克/毫升）阻断。这些观察结果表明，TNF-α可能对胎盘激素合成产生影响，这在正常分娩和早产的发病机制中可能很重要。这些作用中至少有一些似乎是通过新的蛋白质合成介导的。
