Tumor necrosis factor-alpha affects in vitro hormone production by JEG-3 choriocarcinoma cell cultures

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.