Absence of TGF-β Receptor Activation by Highly Purified hCG Preparations

Recently, several LH/human chorionic gonadotropin (hCG) receptor-independent activities for hCG have been described, including activation of the TGF-beta receptor (TGF beta R) by hyperglycosylated hCG and stimulation of trophoblast invasion. Because the hCG concentrations used in these studies have been rather high, reflecting physiological hCG levels in pregnancy, even a minor contamination with growth factors, which act at very low concentrations, may be significant. Several commercial hCG preparations have been found to contain significant amounts of epidermal growth factor (EGF), which we also confirmed here. Furthermore, we found that some hCG preparations also contain significant amounts of TGF-beta 1. These hCG preparations were able to activate ERK1/2 in JEG-3 choriocarcinoma cells or TGF beta R in mink lung epithelial cells transfected with a reporter gene for TGF beta R activation. No such activation was found with highly purified hCG or its free beta-subunit (hCG beta), irrespective of whether they were hyperglycosylated or not. Taken together, our results suggest that the growth factor contaminations in the hCG preparations can cause activation of TGF beta R and, at least in JEG-3 cells, MAPK signaling. This highlights the importance to carefully control for potential contaminations and that highly purified hCG preparations have to be used for biological studies.