TUMOR-NECROSIS-FACTOR-ALPHA INHIBITS HUMAN CHORIONIC-GONADOTROPIN SECRETION

The placenta is a major source of tumor necrosis factor-alpha (TNF-alpha) and is rich in TNF-alpha receptors. TNF-alpha inhibited hCG secretion by normal chorionic villi at 6 weeks gestation, but chorionic villi contain the heterogenous cell population. To investigate the direct effects of TNF-alpha on trophoblasts, the NUC1 choriocarcinoma cell line was used as an in vitro placental cell model. TNF-alpha also inhibited hCG secretion by NUC1 cells at concentrations from 1-100 U/mL. TNF-alpha at concentrations of 1, 10, and 100 U/mL significantly decreased hCG secretion for 24 h to 88%, 81%, and 71% of the control level, respectively. The expression of hCG-beta mRNA was also decreased to 23% of the control level after 24 h of TNF-alpha treatment (100 U/mL). Inhibition occurred after 12 h of TNF-alpha treatment (100 U/mL). Two measurements, trypan blue dye exclusion and 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide reduction, revealed that these inhibitory effects were not due to the cytotoxic activity of TNF-alpha on NUC1. In conclusion, TNF-alpha reduces hCG secretion in vitro.