Concentrations of endothelin-1 in human amniotic fluid at various stages of pregnancy

To examine the possible role of endothelin in the initiation of parturition, endothelin-1-like immunoreactivity (ET-1-LI) in the amniotic fluid (AF) was determined by a sensitive radioimmunoassay (RIA) system. The concentrations of ET-1-LI in AF were 24.7 +/- 6.1 pg/ml (mean +/- SD, n = 6) at the second trimester and were significantly increased to 40.4 +/- 15.1 pg/ml (n = 6) at term. These ET-1-LI concentrations are about three- to fourfold higher than those observed in the maternal plasma. The gel permeation chromatography (GPC) profile of ET-1-LI extracted from second-trimester AF indicated that the ET-1-LI consisted of only one component of 6kET, the molecular weight of which was 6,000, larger than big ET-1. In contrast, ET-1-LI in the AF at term consisted of two components, ET-1 and 6kET. These findings suggest that the level of biologically active ET-1 in the AF increases markedly from second trimester toward term. A significant amount of ET-1-LI was also detected in the supernatant of amnion cell culture. The level of ET-1-LI in the culture medium after 12 h of incubation was almost comparable with that in AF at term. Thus, it is suggested that amnion tissue may be the major source of ET-1-LI in the AF. Together with the fact that ET-1 increases cytoplasmic calcium ion in the target cell, the results of present study raise the possibility that endothelin plays an important role in the initiation of parturition by triggering the production of prostaglandins in fetal membranes.