Action of chicken II GnRH on the human placenta

The stability, receptor binding, bioactivity, and production of chicken II GnRH and its analogs in the human placenta were studied. Both chicken II an d mammalian GnRH are rapidly degraded by placental enzymes, yet the chicken II isoform is six times more stable. Analogs of chicken II GnRH were synth esized, and their stability in the presence of placental enzymes was tested . The D-Arg(6)-chicken II GnRH-aza-Gly(10)-NH2 analog was found to be resis tant to enzymatic degradation. The placental receptor binding activity of t he chicken II GnRH analogs and chicken II GnRH was compared with that of ma mmalian GnRH and its analogs. Because D-Arg(6)-chicken II GnRH-aza-Gly(10)- NH2 had the highest affinity for the placental receptor and was stable in p lacental extracts, the bioactivity of this analog on the regulation of plac ental human CG (hCG) release was compared with that for mammalian and chick en II GnRH using a human term placental explant culture system. This chicke n II GnRH analog effected a stimulation of hCG at the lowest concentration studied (250 nM). With extended exposure and/or higher concentrations of th is chicken II GnRH analog, the release of hCG from human placental explants was inhibited. Using a placental explant perifusion system and a highly sp ecific RIA for chicken II GnRH, the pulsatile release of chicken II GnRH fr om the early human placenta was demonstrated. These studies are the first to demonstrate bioactivity of a second form of GnRH in a human tissue and to identify the pulsatile release of chicken II GnRH from a human tissue. These data led us to propose that chicken II GnRH and its synthetic analogs may be potent ligands for hormone regulation dur ing pregnancy.