Modulation of human cytotrophoblastic leptin secretion by interleukin-1 alpha and 17 beta-oestradiol and its effect on HCG secretion

To investigate the role of leptin during pregnancy, we assessed leptin prod uction by pure cultured human cytotrophoblastic cells (CTB), its regulation by cytokines and 17 beta-oestradiol and its effects on human chorionic gon adotrophin (HCG) secretion. Purified CTB from first trimester placenta were incubated in duplicates in the presence or absence of cytokines or 17 beta -oestradiol. Medium was harvested on day 2 and the culture stopped on day 4 . Results were corrected for protein content of each individual well and ex pressed as percent of controls per day (mean +/- SEM). Basal CTB leptin pro duction was 25.2 +/- 2.6 (ng/mg prot). In comparison with controls, leptin production was stimulated to 320 +/- 16% (P < 0.0001) and 195 +/- 3.2% (P < 0.0004) by 3 and 10 ng/ml of interleukin-1 alpha respectively 17 beta-oest radiol 10(-6) to 10(-9) mol/l increased basal leptin production 5-9-fold, w hile 10(-5) mol/l had no such effect. Basal CTB HCG secretion was 5722 +/- 1055 (mIU/mg prot). There was a dose-dependent leptin-induced increase in H CG secretion (P = 0.0039) reaching a 5-fold increase with a leptin concentr ation of 1 mu g/ml (P < 0.006). Gonadotrophin-releasing hormone (GnRH) 8.5 x 10(-8) mol/l significantly increased HCG secretion to 140 +/- 21% of cont rols (P = 0.031). Cetrorelix (0.1 mu g/ml) inhibited leptin-induced HCG sec retion (P = 0.0028).