Effect of excessive GnRH-binding substance on circulating maternal hCG in human pregnancy

Gonadotropin-releasing hormone (GnRH) can stimulate the release of placental human chorionic gonadotropin (hCG). Thus, at the onset of these studies it was the objective to define the relationship of hCG to GnRH in the maternal circulation throughout pregnancy, focusing on early pregnancy. Blood samples were collected at 8, 10, 12, 14, 16, 28 and 36 weeks of gestation during labor and the GnRH and hCG levels were determined by radioimmunoassay. Of 39 pregnancies, a GnRH-binding substance was found in the maternal circulation of three. This GnRH-binding substance resulted in erroneous GnRH levels, due to the very high non-specific binding. In the pregnant women without this GnRH-binding substance, GnRH attained highest concentrations at 12-14 weeks. The typical peak of hCG at 8-10 weeks of gestation was observed in this group, while the group of patients having the GnRH-binding substance had significantly lower hCG levels. Each of the patients with circulating GnRH-binding substance had prior pregnancy(s) and two of the three had a prior pregnancy loss. The nature of this GnRH-binding substance was investigated using gel chromatography. After incubation of [125I]GnRH with patient plasma for 3 days this substance was shown to be of high molecular weight which was ethanol precipitable. This binding substance may therefore be an antibody, since it appears to be a high molecular weight protein requiring a number of days to bind the [125I] GnRH. This GnRH-binding substance may be of physiological importance, since the circulating hCG level was significantly less in the group of patients with this substance than in those without.