Comparison of the effects of GnRH-I and GnRH-II on HCG synthesis and secretion by first trimester trophoblast

Gonadotrophin-releasing hormone (GnRH) is an important factor in the regulation of the synthesis and secretion of gonadotrophins from the pituitary gland, An isoform of this decapeptide, GnRH-II, with an amino acid sequence 70% homologous to GnRH-I, has been recently described. Since the physiological effects of GnRH-II are not yet known, we undertook the present study to see whether GnRH-II could be involved in the secretion and synthesis of HCG in first trimester trophoblast. We incubated cytotrophoblastic cells (CTB) with GnRH-I or GnRH-II, for 4 or 96 h and collected the media at different times thereafter. We also performed experiments with placental tissue, where GnRH-I or GnRH-II was added to perifused placental explants, and samples were collected every 3 min. Total amounts of human chorionic gonadotrophin (HCG) were measured in all samples by enzyme-linked immunosorbent assay. GnRH-I was more potent than GnRH-II when incubated for 4 h with CTB, as indicated by increased HCG secretion at 8 h and at 24 h. GnRH-I, but not GnRH-II, down-regulated HCG secretion when incubated for 96 h, GnRH-I significantly increased HCG secretion by the explants, while GnRH-II had a lesser effect. Both induced a pulse of HCG immediately after their injection. Our data show that GnRH-I has more effect than GnRH-II on HCG synthesis and secretion. This difference could be explained by different pathways of GnRH degradation, different receptor affinities, or even by different types of placental GnRH receptor.